TWC BioSearch
Signal Transduction Supplier

PROTEIN KINASES

SERINE/THREONINE KINASES

PROTEIN KINASE C

PKC ENZYMES


TABLE 1. PROTEIN KINASE C SUBTYPES


Subtype

MW (kDa)

Activators

Tissue Expression

Refs.

         
Group A, Classical

       
a

76.8

PS, Ca2+, DG, FFA, LPC

Ubiquitous

1,2

bI

76.8

PS, Ca2+, DG, FFA, LPC

Various

1,2

bII

76.9

PS, Ca2+, DG, FFA, LPC

Various

1,2

g

78.4

PS, Ca2+, DG, FFA, LPC

Brain

1,2

         
Group B, New

       
d

77.5

PS,DG

Ubiquitous

3,4,5

e

83.5

PS, DG, FFA

Brain

3,6,7,8

h
78.0

Cholesterol sulfate

Lung, skin, heart

9,10,11

q

81.6

?

Skeletal muscle

12
         
Group C, Atypical

       
z
67.7

PS, FFA, PIP3, Cer

Ubiquitous

9,13,14

l
67.2

?

Ovary, testis

12

Abbreviations: DG, diacylglycerol; PS, phosphatidylserine; FFA, cis unsaturated fatty acid; LPC, lysophosphatidylcholine; Cer, ceramide. Adapted from reference 12.

SE-111
Protein kinase C, calcium- and lipid-dependent (from rat brain)
>95% by SDS-PAGE, MW=76-82 kDa (EC 2.7.1.37) Storage: -70°C
Supplied at 35 µg/ml. Specific activity: >1 µmol phosphate/min/mg enzyme using histone H1 as substrate at pH 7.4 and 22°C. Consists primarily of a, b and g isotypes15,16,17,18.
1.75 µg

SE-133
Protein kinase C, catalytic fragment (PKM) (from rat brain)
>95% by SDS-PAGE, MW=55 kDa, Storage: -70°C
Supplied at 10 µg/ml. Specific activity: 0.8 µmol phosphate/min/mg enzyme using histone H1 as substrate at pH 7.4 and 30°C. This is the catalytically active fragment of rat brain PKC (catalog #SE-111, above) prepared by digestion with trypsin19,20,21. It does not require calcium or phosphatidylserine for its activity.
0.25 µg
5 x 0.25 µg

SE-143
Protein kinase C alpha (PKCa) (human, recombinant)
>95% by SDS-PAGE, MW=76.8 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.5 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~1.5 µmol phosphate/min/mg protein using histone H1 as substrate. Reaction conditions are 10 mM MgCl2, 100 µM CaCl2, 100 µg/ml phosphatidylserine (PS), 20 µg/ml diacylglycerol (DAG), 0.2 mg/ml histone H1, 100 µM ATP and 0.03% Triton X-100 at pH 7.4 and 30°C. Activity of PKCa in the absence of PS and DAG is decreased to <15%. May be used to phosphorylate target substrates of PKCa and to study enzyme regulation and kinetics.
10 µg

SE-144
Protein kinase C beta I (PKCbI) (human, recombinant)
>95% by SDS-PAGE, MW=76.8 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.5 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~0.9 µmol phosphate/min/mg protein using histone H1 as substrate. Reaction conditions are 10 mM MgCl2, 100 µM CaCl2, 100 µg/ml phosphatidylserine (PS), 20 µg/ml diacylglycerol (DAG), 0.2 mg/ml histone H1, 100 µM ATP and 0.03% Triton X-100 at pH 7.4 and 30°C. Activity of PKCbI in the absence of PS and DAG is decreased to <3%. May be used to phosphorylate target substrates of PKCbI and to study enzyme regulation and kinetics22,23,24.
10 µg

SE-146
Protein kinase C gamma (PKCg) (human, recombinant)
>95% by SDS-PAGE, MW=78.4 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.5 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~1.2 µmol phosphate/min/mg protein using histone H1 as substrate. Reaction conditions are 10 mM MgCl2, 100 µM CaCl2, 100 µg/ml phosphatidylserine (PS), 20 µg/ml diacylglycerol (DAG), 0.2 mg/ml histone H1, 100 µM ATP and 0.03% Triton X-100 at pH 7.4 and 30°C. Activity of PKCg in the absence of PS and DAG is decreased to <10%. May be used to phosphorylate target substrates of PKCg and to study enzyme regulation and kinetics.
10 µg

SE-147
Protein kinase C delta (PKCd) (human, recombinant)
>95% by SDS-PAGE, MW=77.5 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.5 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~1.2 µmol phosphate/min/mg protein using PKC epsilon peptide (BIOMOL catalog #P-155) as substrate. Reaction conditions are 10 mM MgCl2, 0.1 mM EGTA, 200 µg/ml phosphatidylserine (PS), 20 µg/ml diacylglycerol (DAG), 0.1 mg/ml substrate, 100 µM ATP and 0.03% Triton X-100 at pH 7.4 and 30°C. May be used to phosphorylate target substrates of PKCd and to study enzyme regulation and kinetics24,25.
10 µg

SE-148
Protein kinase C epsilon (PKCe) (human, recombinant)
>95% by SDS-PAGE, MW=83.5 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.1 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~1.2 µmol phosphate/min/mg protein using PKC epsilon peptide (BIOMOL catalog #P-155) as substrate. Reaction conditions are 10 mM MgCl2, 0.1 mM EGTA, 200 µg/ml phosphatidylserine (PS), 20 µg/ml diacylglycerol (DAG), 0.1 mg/ml substrate, 100 µM ATP and 0.03% Triton X-100 at pH 7.4 and 30°C. May be used to phosphorylate target substrates of PKCe and to study enzyme regulation and kinetics24,25.
10 µg

SE-149
Protein kinase C zeta (PKCz) (human, recombinant)
>95% by SDS-PAGE, MW=67.7 kDa, (EC 2.7.1.37) Storage: -70°C
Highly active enzyme expressed in a baculovirus expression system. Supplied at 0.2 mg/ml in 50% glycerol/stabilizing buffer. Specific activity: ~0.4 µmol phosphate/min/mg protein using PKC epsilon peptide (BIOMOL catalog #P-155) as substrate. Reaction conditions are 5 mM MgCl2, 0.5 mM EGTA, 1 mM DTT, 100 µg/ml phosphatidylserine (PS), 0.1 mg/ml substrate, and 100 µM ATP at pH 7.5 and 30°C. May be used to phosphorylate target substrates of PKCz and to study enzyme regulation and kinetics23,24
10 µg

PKC SUBSTRATES

P-117
MARCKS psd peptide, PKC substrate
Lys-Lys-Lys-Lys-Lys-Arg-Phe-Ser-Phe-Lys-Lys-Ser-Phe-Lys-Leu-Ser-Gly-Phe-Ser-Phe-Lys-Lys-Asn-Lys-Lys
>97%, MW=3078.8 [125267-21-2] Storage: -20°C
Sequence is from myristoylated Ala-rich C-kinase substrate (MARCKS) protein phosphorylated site domain (psd), residues 151-175. Protein kinase C (including PKCe) phosphorylates the peptide at Ser-8, 12 and 19. Poor substrate for PKA, PKG, CaMKI, II, III. Km=20 nM for purified rat brain PKC. Can be used in phosphocellulose, SDS-PAGE or anion exchange assays26,27,28.
1 mg
5 x 1 mg

P-155
Protein kinase C epsilon substrate
Glu-Arg-Met-Arg-Pro-Arg-Lys-Arg-Gln-Gly-Ser-Val-Arg-Arg-Arg-Val
>97%, MW=2066.2, Storage: -20°C
PKC epsilson pseudosubstrate sequence (149-164) but Ala to Ser-159 substitution makes it a substrate for phosphorylation29. Phospholipid/phorbol ester-dependent substrate for PKC e and z 6,14.
0.5 mg
5 x 0.5 mg

P-110
MBP (4-14), N-acetylated, protein kinase C substrate
N-Acetyl-Gln-Lys-Arg-Pro-Ser-Gln-Arg-Ser-Lys-Tyr-Leu
>97%, MW=1432.8 [126768-94-3] Storage: -20°C
Sequence is from myelin basic protein (4-14)30. Specific substrate for a-,b-, g-isoforms of PKC (Km=7 µM) and poor substrate for PKA, CaMKII, CKI, CKII, and phosphorylase kinase. This N-acetylated peptide is resistant to phosphatases in brain hippocampal extracts and therefore is a good substrate for use in crude extracts31.
1 mg
5 x 1 mg

P-109
EGF-R fragment (651-658), protein kinase substrate
Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu
>97%, MW=1098.5, Storage: -20°C
Epidermal growth-factor receptor (EGF-R) conserved sequence which is identical to v-erb-B (95-102). Sequence includes EGF-R Thr-654 PKC phosphorylation site32.
1 mg
5 x 1 mg

P-111
Protein kinase C [Ser-25] (19-31), substrate
Arg-Phe-Ala-Arg-Lys-Gly-Ser-Leu-Arg-Gln-Lys-Asn-Val
>97%, MW=1560, Storage: -20°C
PKC pseudosubstrate sequence but Ala to Ser-25 substitution makes it a good substrate (Km=0.2 µM) rather than an inhibitor33,34.
1 mg
5 x 1 mg


PKC ACTIVATORS

PHORBOL ESTERS

Phorbol esters such as phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-dibutyrate (PDBu), and phorbol 12,13-didecanoate (PDD) bind to and activate protein kinase C. At nanomolar concentrations, they dramatically increase the affinity of the enzyme for Ca2+ resulting in its full activation35-39. Phorbol esters with 4a stereochemistry are inactive and may be used as negative controls40.
WARNING! Potential health hazard: Phorbol esters are vesicants. Irritation and blistering may result from skin contact. Use of these compounds should be restricted to technically qualified personnel.


PE-187
12-Deoxyphorbol 13-acetate (Prostratin)
99%, MW=390.5 [60857-08-1] Storage: -20°C
A non-tumor promoting phorbol ester which acts as a PKC partial agonist. Protects T-lymphoblastoid cells from the killing effects of HIV-141.
1 mg
5 mg

PE-182
12-Deoxyphorbol 13-phenylacetate 20-acetate (dPPA)
99%, MW=508.6 [54662-30-5] Storage: -20°C
dPPA is a selective activator of PKCb1. It is at least 1000-fold more potent for the b1 isozyme than the a, g, d or e isozymes but activates the isozyme to only 60% of maximal activity42,43. Mimicks the effect of TNFa on endothelial cells but does not translocate PKC44.
1 mg
5 mg

PE-135
Phorbol 12,13-dibutyrate
99%, MW=504.6 [37558-16-0] Storage: -20°C
PKC activator35 (10-100 ng/ml).
1 mg
5 mg

PE-140
4a-Phorbol 12,13-dibutyrate
99%, MW=504.6 [93781-54-5] Storage: -20°C
Negative control for phorbol 12,13-dibutyrate.
1 mg
5 mg

PE-145
Phorbol 12,13-didecanoate
99%, MW=672.9 [24928-17-4] Storage: -20°C
PKC activator35 (10-100 ng/ml).
1 mg
5 mg

PE-147
4a-Phorbol 12,13-didecanoate
99%, MW=672.9 [27536-56-7] Storage: -20°C
Negative control for phorbol 12,13-didecanoate35.
1 mg
5 mg

PE-160
Phorbol 12-myristate 13-acetate (PMA)
(12-tetradecanoyl phorbol 13-acetate, TPA)
99%, MW=616.8 [16561-29-8] Storage: -20°C
PKC activator35,42 (10-100 ng/ml).
1 mg
5 mg

PE-162
4a-Phorbol 12-myristate 13-acetate
99%, MW=616.8 [63597-44-4] Storage: -20°C
Negative control for phorbol 12-myristate 13-acetate (PMA).
1 mg
5 mg


DIACYLGLYCEROLS AND RELATED PRODUCTS

A variety of natural and unnatural diacylglycerols (DAG) bind to and activate protein kinase C38,45,46. Activation by diacylglycerols is transient due to their rapid conversion by diacylglycerol kinase47 and lipase48. Diacylglycerols with various fatty acids in the 1,2-sn configuration are active, with those having an unsaturated fatty acid being most active45,49,50. The other isomers, 2,3-sn-diacylglycerol and l,3-diacylglycerol, neither activate nor inhibit the enzyme51. Activation of protein kinase C by diacylglycerols is synergistic with cis-unsaturated fatty acids52. Diacylglycerols play important roles in growth factor signal transduction53.

SE-100
Diacylglycerol kinase (from E. coli)
sn-1,2-diacylglycerol kinase (DAGK)
MW=13.7 kDa, [93076-89-2] (EC 2.7.1.107) Storage: -20°C
Supplied as a turbid membrane suspension with protein concentration of 1 mg/ml. Specific for sn-1,2 isomer of DAG but will phosphorylate ceramide and monoglycerol at a lower rate. Specific activity is >5 U/mg protein for DAG. One unit is the amount of enzyme that will phosphorylate 1.0 mmol of diacylglycerol per minute at 25°C54. Specific activity for ceramide phosphorylation is ~0.5 mmol ceramide/min/mg protein at 25°C. Can be used to quantify diacylglycerol and ceramide in crude lipid extracts55,56.
1 mg
5 x 1 mg

DG-100
(?1,2-Didecanoylglycerol (10:0)
98%, MW=400.6 [82950-64-9] Storage: -20°C
A membrane permeable but non-physiologic DAG57. Stimulates protein kinase C in intact platelets50.
20 mg
100 mg

DG-112
1,2-Dioctanoyl-sn-glycerol (8:0)
98%, MW=344.5, [75685-80-2] Storage: -20°C
A membrane permeable but non-physiologic DAG50. Induces a discrete but transient translocation of protein kinase C58.
20 mg
100 mg

DG-115
(?1,2-Dioleoylglycerol (18:1)
98%, MW=621.0 [3738-74-7] Storage: -20°C
PKC activator.
20 mg
100 mg

DG-125
1-Oleoyl-2-acetyl-sn-glycerol (OAG)
98%, MW=398.6 [86390-77-4] Storage: -20°C
A potent, membrane permeable, non-physiologic DAG which activates protein kinase C45,46.
25 mg
100 mg

DG-130
1-Stearoyl-2-arachidonoyl-sn-glycerol
98%, MW=645.0, [65914-84-3] Storage: -20°C
Putative endogenous activator of protein kinase C produced via receptor mediated inositol phospholipid hydrolysis50.
10 mg
50 mg

DG-135
1-Stearoyl-2-linoleoyl-sn-glycerol
98%, MW=621.0, Storage: -20°C
Putative endogenous activator of protein kinase C produced via receptor mediated inositol phospholipid hydrolysis50.
20 mg
100 mg

DG-140
1-O-Hexadecyl-2-O-arachidonoyl-sn-glycerol
98%, MW=603.0, Storage: -20°C
Hexadecylether analog of DG-130.
5 mg
25 mg

EI-136
R 59022
99%, MW=459.9 [93076-89-2] Storage: RT
R 59022 amplifies protein kinase C activity via inhibition of diacylglycerol kinase. It inhibits human platelet DAG kinase in intact cells (IC50=3.6 µM) and in isolated membranes (IC50=6.7 µM)59,60. In porcine thymus cytosol it inhibited the 80 kDa DAG kinase (IC50=10 µM) with no effect on the 150 kDa DAG kinase61.
10 mg
50 mg

EI-202
R 59949
99%, MW=489.6 [120166-69-0] Storage: 0°C
R 59949 is a more potent analog of R 59022. It inhibits human platelet DAG kinase in intact cells (IC50=0.12 µM) and in isolated membranes (IC50=0.3 µM)62.
10 mg
50 mg

ST-300
RHC-80267
Diacylglycerol lipase inhibitor.



OTHER PKC ACTIVATORS

ST-103
Bryostatin 1
99%, MW=887.0 [83314-01-6] Storage: -20°C
A structurally unique marine natural product that binds to and activates PKC at picomolar concentrations but is not a carcinogen or a complete tumor promoter63. In many systems it induces only a subset of the responses to PMA and blocks those which it does not induce64. It is markedly more potent than PMA for translocating PKCd and e64.
10 µg
5 x 10 µg

PE-190
Farnesyl thiotriazole
98%, MW=305.5 [156604-45-4] Storage: -20°C
A structurally unique activator of PKC in whole cells or in purified enzyme preparations (KD=2.5 µM) which is equipotent with dioleylglycerol65. Since it does not possess hydrolyzable esters of fatty acids, it represents a new stable, persistent PKC activator.
10 mg
50 mg

PE-186
Ingenol 3,20-dibenzoate
97%, MW=556.7 [59086-90-7] Storage: -20°C
Ingenol is a diterpenoid related to phorbol. Ingenol 3,20-dibenzoate competes with [3H]phorbol dibutyrate for binding to PKCa (Ki for binding=240 nM)66.
1 mg
5 mg

PE-174
(-)-7-Octylindolactam V
99%, MW=413.6 [109346-66-9] Storage: -20°C
Octylindolactam V is a non-phorbol protein kinase C activator related to teleocidin. The advantages of octylindolactam V include greater metabolic stability and high potency67,68 (inhibition of PMA binding: EC50=29 nM).
1 mg
5 mg

PE-176
(+)-7-Octylindolactam V
99%, MW=413.6 [123597-54-6] Storage: -20°C
A biologically inactive isomer which may be used as a negative control.
1 mg
5 mg

EI-143
SC-10
N-Heptyl-5-chloronaphthalene-1-sulfonamide
99%, MW=339.9 [102649-79-6] Storage: RT
Activates protein kinase C. Stimulates protein kinase C mediated myosin light chain phosphorylation without activating MLC kinase69.
10 mg
50 mg

PE-184
Thymeleatoxin
99%, MW=628.7, Storage: -20°C
Thymeleatoxin is a diterpene isolated from Thymelea hirsuta L. It activates PKC isozymes a, bI and g selectively (ED50 100 nM) over the d and e isozymes42,43.
1 mg
5 mg


PKC INHIBITORS

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES

ISOTYPE-SELECTIVE PKC INHIBITORS

EI-269
G?6976
95%, MW=378.4 Storage: -20?/font>C
G?6976 inhibits PKCa (IC50=2.3 nM) and PKCb1 (IC50=6.2 nM) but has no effect on d, e or z isotypes70.
500 mg
5 x 500 mg

EI-270
Rottlerin
98%, MW=516.6 [82-08-6] Storage: -20?/font>C
Inhibits PKCd (IC50=3-6 mM) 5-10 fold more potently than a and b and 13-33 fold more potently than e, z and h71.
10 mg
50 mg

EI-273
HBDDE
2,2',3,3'4,4'-Hexahydroxy-1,1'-biphenyl-6,6'-dimethanol dimethyl ether
97%, MW=338.4 Storage: -20?/font>C
Inhibits PKCa (IC50=43 mM) and PKCg (IC50=50 mM) without inhibiting the d, bI and bII isotypes72.
1 mg
5 mg

PAN-SPECIFIC PKC INHIBITORS

EI-198
Calphostin C (UCN-1028C)
99%, MW=790.6 [121263-19-2] Storage: 0°C
Calphostin C is a novel, potent and highly selective inhibitor of protein kinase C (IC50=0.05 µM)73,74. Inhibition is via interaction with the regulatory domain75 and is light dependent76. See Table 4 for selectivity data.
100 µg
1 mg

EI-225
Chelerythrine chloride
98%, MW=383.8 [3895-92-9] Storage: 0°C
A potent and selective inhibitor of protein kinase C77 (IC50=0.66 µM). See Table 4 for selectivity data.
5 mg
25 mg

EI-246
GF 109203X
98%, MW=412.5 [133052-90-1] Storage -20°C
GF 109203X is a potent and selective protein kinase C inhibitor which has been used effectively in platelets, Swiss 3T3 fibroblasts78 and macrophages79. Inhibitory profile: PKC, IC50=0.02 µM (inhibits a, bI, bII and g subtypes with similar potency); PKA, IC50=2.0 µM; phosphorylase kinase, IC50=0.7 µM; insulin, EGF and PDGF receptor tyrosine kinases are not inhibited at concentrations up to 50 µM78.
1 mg
5 x 1 mg

EI-149
(?1-O-Hexadecyl-2-O-methylglycerol
99%, MW=330.6, Storage: 0°C
Inhibits protein kinase C activation by diacylglycerols80,81. Inhibits the fMLP or phorbol ester-induced respiratory burst in human neutrophils82.
50 mg
250 mg

EI-150
1-O-Hexadecyl-2-O-acetyl-sn-glycerol
Inhibits protein kinase C activation by diacylglycerols.

EI-226
Hypericin
99%, MW=504.4 [548-04-9] Storage: 0°C
A potent and selective inhibitor of protein kinase C136 (IC50=3.4 µM) which also possesses antiviral activity83. See Table 4 for selectivity data.
1 mg
5 mg

EI-154
Phloretin
99%, MW=274.3 [60-82-2] Storage: 0°C
Inhibits protein kinase C. Completely inhibits transformation of BALB/3T3 cells at 30 µg/ml84.
200 mg
1 g

EI-155
Sphingosine
Inhibits protein kinase C activity and phorbol dibutyrate binding in human platelets.
See Sphingolipids

P-205
Myristoylated protein kinase C (18-28), cell-permeable PKC inhibitor
N-Myr-Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln
>97%, MW=1256.0, Storage: -20°C
Pseudosubstrate sequence from PKCa and b. Highly specific inhibitor which is N-terminal myristoylated to allow membrane permeability. IC50=8 µM for TPA activation of MARCKS phosphorylation in fibroblast primary cultures, and 98% inhibition at 100 µM85. Partially reverses multidrug resistance in human breast cancer cells86.
0.5 mg
5 x 0.5 mg

P-207
Myristoylated EGF-R fragment (651-658), PKC inhibitor
N-Myr-Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu
>97%, MW=1308.1, Storage: -20°C
Epidermal growth-factor receptor (EGF-R) conserved sequence which is identical to v-erb-B (95-102). This inhibitor is N-terminal myristoylated to allow membrane permeability and inhibits protein kinase C in intact cells (IC50=5 µM)87,88.
0.5 mg
5 x 0.5 mg

P-206
Protein kinase C (19-31), pseudosubstrate inhibitor
Arg-Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln-Lys-Asn-Val
>97%, MW=1544, Storage: -20°C
Shorter and more potent inhibitor of PKC (IC50=100 nM) than longer sequence (19-36)33.
1 mg
5 x 1 mg

P-150
Protein kinase C pseudosubstrate (19-36), inhibitor
Arg-Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln-Lys-Asn-Val-His-Glu-Val-Lys-Asn
>97%, MW=2151.8, Storage: -20°C
Corresponds to PKC pseudosubstrate regulatory sequence89. Potent and selective PKC inhibitor which binds to the active site of the kinase. IC50 for purified brain PKC=0.18 µM, PKA=423 µM, MLCK=24 µM33,34.
0.5 mg
5 x 0.5 mg

PKC ANTIBODIES

SA-143
Anti-Protein kinase C
Mouse monoclonal antibody. Clone MC5. Supplied as affinity purified IgG2a, 0.1 mg/ml. Recognizes Ca2+/phospholipid dependent protein kinase C (a, b and g isotypes) in human, rat and mouse. Epitope is at the hinge region of the enzyme, the site of phorbol ester induced cleavage90. Applications: WB 1/100, IF 1/10 and other techniques.
100 µg

SA-144
Anti-Protein kinase C a
Rabbit polyclonal antibody. Immunogen: Rabbit PKC a (662-672) peptide. Supplied as serum. Cross-reacts with human, rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-144
Anti-Protein kinase C a (SA-144) control peptide
Control peptide CQFVHPILQSSV is useful to block specific staining by WB with SA-144, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-145
Anti-Protein kinase C b1
Rabbit polyclonal antibody. Immunogen: Human PKC bI (661-671) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-145
Anti-Protein kinase C b1 (SA-145) control peptide
Control peptide CSYTNPEFVINV is useful to block specific staining by WB with SA-145, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-146
Anti-Protein kinase C bII
Rabbit polyclonal antibody. Immunogen: Human PKC b II (661-673) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-146
Anti-Protein kinase C bII (SA-146) control peptide
Control peptide CFVNSEFLKPEVKS is useful to block specific staining by WB with SA-146, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg


SA-147
Anti-Protein kinase C g
Rabbit polyclonal antibody. Immunogen: Human PKC g (681-697) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-147
Anti-Protein kinase C g (SA-147) control peptide
Control peptide CVHPDARSPISPTPVPVM is useful to block specific staining by WB with SA-147, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg


SA-148
Anti-Protein kinase C d
Rabbit polyclonal antibody. Immunogen: Human PKC d (658-676) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-148
Anti-Protein kinase C d (SA-148) control peptide
Control Peptide CSAFAGFSFVNP is useful to block specific staining by WB with SA-148, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-149
Anti-Protein kinase C e
Rabbit polyclonal antibody. Immunogen: Human PKC e (721-737) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-149
Anti-Protein kinase C e (SA-149) contol peptide
Control peptide CNQEEFKFSYFGED is useful to block specific staining by WB with SA-149, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-150
Anti-Protein kinase C
Rabbit polyclonal antibody. Immunogen: Human PKC (721-737) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-150
Anti-Protein kinase C (SA-150) contol peptide
Control peptide CFEGFEYINPLLLSTEESV is useful to block specific staining by WB with SA-150, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-151
Anti-Protein kinase C
Rabbit polyclonal antibody. Immunogen: Human PKC (666-683) peptide. Supplied as serum. Cross-reacts with rat, mouse and other mammalian species. Applications: WB 1/100.
1 ml

SP-151
Anti-Protein kinase C (SA-151) control peptide
Control peptide CNQDEFRNFSYVSPELQP is useful to block specific staining by WB with SA-151, above. Supplied at 0.2 mg/ml in ammonium bicarbonate buffer.
100 µg

SA-183
Anti-Protein kinase C set
Contains 0.5 ml each of SA-144, SA-145, SA-146, SA-147, SA-148, SA-149, SA-150, SA-151.
1 set

SP-183
PKC peptide set
Contains 100 µg each of SP-144, SP-145, SP-146, SP-147, SP-148, SP-149, SP-150, and SP-151
1 set



PROTEIN KINASE A (PKA)

PKA ENZYMES

SE-110
Protein kinase A, a catalytic subunit (from porcine heart)
3',5'-cyclic AMP dependent protein kinase
MW=38 kDa, Storage: -20°C
Partially purified preparation, supplied lyophilized. Specific activity: 30-65 U/µg protein. One unit will add 1 pmol phosphate to dephosphorylated casein per minute at pH 6.5 and 30°C. cAMP is not necessary for activity. Useful to phosphorylate peptides for use as substrates in Ser/Thr phosphatase assays 92,94.
1000 U

SE-122
Protein kinase A, a catalytic subunit (murine, recombinant)
3',5'-cyclic AMP dependent protein kinase
MW=38 kDa, Storage: -20°C
Expressed in E. coli91. Contains no detectable protease or phosphatase activity. Supplied at ~1 mg/ml in 50% glycerol buffer. Specific activity: >1000 U/mg protein. One unit will add 1 nmol phosphate to Kemptide peptide substrate (catalog #P-107, below) per minute at pH 7.5 and 30°C. Regulatory subunit is not present, therefore cAMP is not necessary for activity. Useful to phosphorylate target regulatory enzymes and other substrates of PKA.
50 U
5 x 50 U


TABLE 2. PROTEIN KINASE A ACTIVATORS: CYCLIC AMP ANALOGS*

Catalog #

Analog

Comments

Page #

CN-115

8-Bromo-cAMP

Activates PKA, more resistant to PDE's than cAMP.

000

CN-136

Sp-cAMPS

Activates PKA, completely resistant to PDE's, half-maximal activation at 1.8 µM.

000

CN-130

8-CPT cAMP

Activates PKA and PKG.

000

CN-125

Dibutyryl-cAMP

Preferentially activates PKA.

000

CN-120

Sp-5,6-DCl-cBiMPS

Specific activator of PKA, resistant to PDE's.

000

* All of these reagents are cell-permeable.
Abbreviations: PDE's = phosphodiesterases.

SEE CYCLIC AMP ANALOGS, ADENYLATE CYCLASE ACTIVATORS AND INHIBITORS AND PHOSPODIESTERASE INHIBITORS FOR OTHER PKA RELATED REAGENTS.


PKA SUBSTRATES

P-118
[Ala-97]-RII (81-99), PKA substrate
Asp-Leu-Asp-Val-Pro-Ile-Pro-Gly-Arg-Phe-Asp-Arg-Arg-Val-Ser-Val-Ala-Ala-Glu
>97%, MW=2112.4, Storage: -20°C
Sequence is from cAMP-dependent protein kinase regulatory subunit type II (PKA). The phosphorylated peptide can be used as a substrate for calcineurin92,93,94.
0.5 mg
5 x 0.5 mg

P-106
H1-7 (histone H1 phosphorylation site), PKA substrate
Arg-Arg-Lys-Ala-Ser-Gly-Pro
>97%, MW=770.9 [65189-70-0], Storage: -20°C
Sequence is derived from calf thymus histone H1 containing Ser-38. Peptide is phosphorylated by protein kinase A95.
1 mg
5 x 1 mg

P-107
Kemptide, protein kinase substrate
Leu-Arg-Arg-Ala-Ser-Leu-Gly
>97%, MW=771.9 [65189-71-1] Storage: -20°C
Substrate for Ser/Thr protein kinases. Km=4.7 µM for PKA96,97,98.
1 mg
5 x 1 mg

P-108
Malantide, protein kinase substrate
Arg-Thr-Lys-Arg-Ser-Gly-Ser-Val-Tyr-Glu-Pro-Leu-Lys-Ile
>97%, MW=1634.1 [86555-35-3] Storage: -20°C
Sequence is from site of phosphorylation by PKA on the b-subunit of phosphorylase kinase. Highly specific substrate for cAMP-dependent protein kinase (PKA)99. PKI inhibited >90% substrate phosphorylation in various tissue extracts100. Km=15 µM for PKA; 223 µM for PKG.
1 mg
5 x 1 mg


PKA INHIBITORS

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES)

EI-196
H-89
N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide?HCl
99%, MW=519.2 [127243-85-0] Storage: 0°C
H-89 is a potent, selective101 and widely used102,103 inhibitor of PKA (Ki=48 nM). See Table 4 for selectivity data.
5 mg
25 mg

EI-199
KT5720
98%, MW=537.6 [108068-98-0] Storage: 0°C
KT5720 is a hexylester derivative of K-252a and is a selective inhibitor of PKA (Ki=0.056 µM)193,104. See Table 4 for selectivity data.
100 µg
5 x 100 µg

EI-158
H-8
N-[2-(Methylamino)ethyl]-5-isoquinolinesulfonamide?HCl
99%, MW=338.3 [84478-11-5] Storage: 0°C
H-8 inhibits PKA and PKG selectively over PKC and MLCK190,105. See Table 4 for selectivity data.
10 mg
50 mg

EI-184
HA-1004
N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide?HCl
98%, MW=329.8 [91742-10-8] Storage: 0°C
HA-1004 inhibits PKA and PKG selectively over PKC and MLCK190. See Table 4 for selectivity data. May be used in conjunction with H7 to probe for PKC-specific effects106.
10 mg
50 mg

EI-233
HA-1077
1-(5-Isoquinolinesulfonyl)-homopiperazine·HCl
98%, MW=327.8 [103745-39-7] Storage: 0°C
HA-1077 inhibits PKA and PKG selectively over MLCK107,108. See Table 4 for selectivity data. Potent vasodilator109.
10 mg
50 mg

SE-123
PKI, Heat-stable inhibitor of cAMP-dependent protein kinase (Rabbit muscle, recombinant)
MW=8 kDa, Storage: -20°C
Native protein (77 amino acid) with an additional N-terminal Met and Gly, expressed in E. coli110. Contains no detectable protease or phosphatase activity. Supplied at 0.8 mg/ml in 50% glycerol buffer. Specific activity: 2250 U/mg protein. One unit will inhibit 1 unit of PKA activity as defined by product SE-122. Ki for PKA catalytic subunit = 0.1 nM. Selective for PKA111.
50 U
5 x 50 U

P-203
PKI (5-24), cAMP-dependent protein kinase inhibitor
Thr-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile-His-Asp
>97%, MW=2222.7 [99534-03-9] Storage: -20°C
Sequence is from the heat-stable skeletal muscle inhibitor protein of PKA. Peptide binds to the catalytic subunit of PKA and displaces the regulatory subunit. Mimics protein substrate by binding to the catalytic site via the Arg-cluster basic residues. Ki =2.3 nM for PKA112,113.
0.5 mg
5 x 0.5 mg

P-204
PKI(6-22) amide, cAMP-dependent protein kinase inhibitor
Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile-NH2
>97%, MW=1868.1 [121932-06-7] Storage: -20°C
Competitive inhibitor of PKA (Ki =1.7 nM)114,115.
1 mg
5 x 1 mg

P-210
Myristoylated PKI (14-22) amide, cell-permeable PKA inhibitor
>97%, MW=1208.9 Storage: -20°C
Heat-stable protein kinase inhibitor (PKI) peptide sequence (14-22)115. N-terminal is myristoylated to increase cell membrane permeability85,88. The non-myristoylated version of this peptide is a highly specific inhibitor of cAMP-dependent protein kinase (PKA) with Ki=36 nM115. This product is a new useful tool for studying PKA in cellular systems.
0.5 mg
5 x 0.5 mg

CN-135
Rp-cAMPS
Rp-Adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPS)
Rp-cAMPS is a potent and specific competitive inhibitor of the activation of cAMP dependent protein kinases by cAMP116 (IC50=4.9 µM)117.

PKA ANTIBODIES

SA-195
Anti-Protein kinase A, RII subunit
Mouse monoclonal antibody. Clone R-30. Immunogen: Purified bovine brain regulatory subunit RII of cAMP-dependent protein kinase118. Supplied as affinity purified IgG2a, 1 mg/ml. Epitope is N-terminal non-conserved region of RII (1-91). Cross-reacts with porcine and to a lesser extent human, rat, and mouse. Antibody enhances binding of RII for cAMP, and does not interfere with the association of RII and C subunits. Applications: WB, IF, ELISA.
250 µg

SW-107
Bovine Heart Extract, Immunoblotting standard
Heart extract purified from cow. Supplied as tissue extract (approximately 0.5 mg/ml) in SDS-PAGE sample buffer, ready-to-use at 2-5 µl (~1-2.5 µg) per lane. Useful as a Western blotting control for anti-protein kinase A, RII subunit (SA-195, above), or for use with other antibodies.
200 µl

SA-270
Anti-Protein kinase A, RIIb subunit (PKA, RIIb)
Rabbit polyclonal antibody. Immunogen: Mouse protein kinase A, regulatory subunit RIIb, N-terminal peptide conjugated to KLH. Supplied as serum. Recognizes human, rat and mouse 52 kDa PKA RIIb. It does not crossreact with PKA RIa, RIb, or RIIa. Applications: WB 1/1000 (alkaline phosphatase), IF and IP119,120.
100 µl

SA-271
Anti-Protein kinase A, RIIb subunit (PKA, RIIb), purified
Rabbit polyclonal antibody. Identical to SA-270 above, but supplied as protein A purified IgG.
100 µg

SP-270
Anti-PKA RIIb (SA-270, -271) control peptide
>90%, MW=1980.0 Storage: -20°C
Immunization and blocking peptide for SA-270 and -271 above. Useful to block specific staining by WB with anti-PKA RIIb antibody (SA-270 and -271, above). Supplied at 1 mg/ml in PBS.
100 µg

SW-103
Rat Brain Extract, Immunoblotting Standard
Whole brain protein extract from rat. Supplied as tissue extract (approximately 5 mg/ml) in SDS-PAGE sample buffer, ready-to-use at 5 µl/lane. Useful as a Western blotting control for PKA RIIb antibody (SA-270 and -271, above), or for use with other antibodies.
200 µl

SW-104
Mouse Brain Extract, Immunoblotting Standard
Whole brain protein extract from mouse. Similar to SW-103 above, but from mouse.
200 µl


PROTEIN KINASE G (PKG)

PKG ENZYME

SE-118
Protein kinase G (from bovine lung)
cGMP-dependent protein kinase
90%, Storage: -70°C
Specific activity: 1-2.5 kU/µg protein, 10-20 pmol cGMP bound/µg. One unit will transfer 1 pmol phosphate to RKRSRAE peptide substrate per minute122,121.
6 kU
5 x 6 kU

TABLE 3. PROTEIN KINASE G ACTIVATORS: CYCLIC GMP ANALOGS*

Catalog #

Analog

Comments

Page #

CN-206

Rp-8-pCPT-cGMPS

PKG antagonist (Ki=0.5 µM), and is resistant to PDE's.

000

CN-216

Rp-8-Br-cGMPS

PKG antagonist, and is resistant to PDE's.

000

CN-205

8-Bromo-cGMP

PKG activator, more resistant to PDE's than cGMP.

000

CN-207

Sp-8-pCPT-cGMPS

Activates PKA and PKG; cGMP mimetic.

000

CN-215

Dibutyryl-cGMP

Preferentially activates PKG.

000

CN-120

Sp-5,6-DCl-cBiMPS

Specific activator of PKA, resistant to PDE's.

000

CN-217

Sp-8-Br-cGMPS

Activates PKA and PKG; cGMP mimetic.

000

* All of these reagents are cell-permeable.
Abbreviations: PDE's = phosphodiesterases.

SEE CYCLIC GMP ANALOGS, GUANYLATE CYCLASE ACTIVATORS AND INHIBITORS AND PHOSPODIESTERASE INHIBITORS FOR OTHER PKG RELATED REAGENTS.


PKG SUBSTRATE

P-112
BPDEtide, cGMP-dependent protein kinase (PKG) substrate
Arg-Lys-Ile-Ser-Ala-Ser-Glu-Phe-Asp-Arg-Pro-Leu-Arg
>97%, MW=1575, Storage: -20°C
Sequence derived from bovine lung cGMP specific phosphodiesterase (cG-BPDE). Specific substrate for PKG, Km=68 µM; Km for PKA=320 µM, and no phosphorylation detected for CaMKII or PKC122,123.
1 mg
5 x 1 mg


PKG INHIBITORS

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES)

EI-200
KT5823
98%, MW=495.5 [126643-37-6] Storage: 0°C
KT5823 is a derivative of K-252a and is a selective inhibitor of PKG (Ki=0.234 µM)193. See Table 4 for selectivity data.
100 µg
5 x 100 µg

EI-158
H-8
N-[2-(Methylamino)ethyl]-5-isoquinolinesulfonamide?HCl
See "PKA inhibitors".

EI-184
HA-1004
N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide?HCl
See "PKA inhibitors".

EI-233
HA-1077
1-(5-Isoquinolinesulfonyl)-homopiperazine·HCl
See "PKA inhibitors".

P-208
PKG inhibitor
Arg-Lys-Arg-Ala-Arg-Lys-Glu
>97%, MW=943.1 [82801-73-8] Storage: -20°C
Sequence is histone H2B (29-35) non-phosphorylatable analog (Ser to Ala-32) of substrate peptide of PKG. Ki =86 µM for PKG; Ki =550 µM for PKA.
1 mg
5 x 1 mg

CaM KINASE II (CaMKII)

CaMKII ENZYME

SE-134
CaM Kinase II (Ca2+/calmodulin-dependent protein kinase II) (from rat brain)
>95% by SDS-PAGE, MW=650 kDa (EC 2.7.10.-) Storage: -70°C
Composed of 60 and 50 kDa subunits in ratios of 1:3 to 1:4. Supplied at 20 µg/ml. Specific activity: 0.9 µmol phosphate/min/mg using synapsin I as substrate at 30°C. Standard assay conditions are 50 mM HEPES, pH 7.4, 10 mM MgCl2, 100 µM ATP, 5 mM CaCl2, 30 µg/ml calmodulin (catalog #SE-101) and 0.6 ng/µl CaM kinase II in a total volume of 50 µl125-127.
0.5 µg
5 x 0.5 µg


CaMKII SUBSTRATES

P-101
Autocamtide-2, protein kinase substrate
Lys-Lys-Ala-Leu-Arg-Arg-Gln-Glu-Thr-Val-Asp-Ala-Leu
>97%, MW=1526.9, Storage: -20°C
Sequence derived from Ca2+/calmodulin-dependent protein kinase II autophosphorylation site RQETVD plus basic residues to facilitate phosphocellulose binding. Contains consensus sequence R-X-X-S/T. Highly selective CaMKII substrate (Km=2 µM for CaMKII; >50 µM for PKC; No activity towards PKA)128.
1 mg
5 x 1 mg

P-102
Syntide-2, protein kinase substrate
Pro-Leu-Ala-Arg-Thr-Leu-Ser-Val-Ala-Gly-Leu-Pro-Gly-Lys-Lys
>97%, MW=1507.8 [108334-68-5] Storage: -20°C
Phosphorylation site 2 of glycogen synthase containing the R-X-X-S/T consensus phosphorylation site129. Substrate for CaMKII (Km =12 µM) with purified enzyme or in cell extracts using TCA/phosphocellulose assay. Substrate for other kinases thus inhibitors must be used to discern activity130. Reported substrate for Raf-1131-133.
1 mg
5 x 1 mg

P-100
CaM kinase IV substrate (peptide-g)
Lys-Ser-Asp-Gly-Gly-Val-Lys-Lys-Arg-Lys-Ser-Ser-Ser-Ser
>97%, MW=1450.8, Storage: -20°C
Sequence from Ca2+/calmodulin-dependent protein kinase II-g (345-358). Substrate is specific for CaMKIV (Km=8 µM) and is a poor substrate for type II. Useful with purified enzyme and crude extracts using phosphocellulose assay134.
1 mg
5 x 1 mg


CaMKII INHIBITORS

SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES)

EI-232
HDBA
2-Hydroxy-5-(2,5-dihydroxybenzylamino)benzoic acid
98%, MW=275.3, Storage: -20°C
Inhibits Ca2+/calmodulin kinase II (IC50=0.2 µM)135. Also inhibits EGF receptor tyrosine kinase (IC50=0.044 µM)136 and pp60c-src(+) kinase (IC50=0.5 µM)135.
2 mg
10 mg

EI-230
KN-62
98%, MW=721.9 [127191-97-3] Storage: 0°C
KN-62 is a potent and selective inhibitor of Ca2+/calmodulin kinase II (Ki=0.9 µM). See Table 4 for selectivity data. Causes cells to arrest in S phase138. In HEK-293 cells expressing type III adenylyl cyclase (III-AC), 10 µM blocked CaMKII phosphorylation of III-AC139 and inhibited hormone-stimulated Ca2+ oscillations140.
1 mg
5 x 1 mg

EI-268
KN-93
95%, MW=501.0 Storage: -20°C
KN-93 is a potent, selective and cell-permeable inhibitor of CaM kinase II (IC50 = 370 nM). Does not significantly inhibit PKA141. Causes cell-cycle arrest in NIH 3T3 fibroblasts142 and HeLa cells143.
1 mg

EI-201
KT5926
98%, MW=525.5 [126643-38-7] Storage: 0°C
KT5926 is a propylether derivative of K-252a193. It inhibits a number of kinases193,144 but is most selective for CaM kinase II (Ki=4.4 nM)195. See Table 4 for selectivity data.
100 µg
5 x 100 µg

P-200
CaM kinase II (290-309), calmodulin antagonist
Leu-Lys-Lys-Phe-Asn-Ala-Arg-Arg-Lys-Leu-Lys-Gly-Ala-Ile-Leu-Thr-Thr-Met-Leu-Ala

P-201
CaM kinase II (281-309), inhibitor
Met-His-Arg-Gln-Glu-Thr-Val-Asp-Cys-Leu-Lys-Lys-Phe-Asn-Ala-Arg-Arg-Lys-Leu-Lys-Gly-Ala-Ile-Leu-Thr-Thr-Met-Leu-Ala
>97%, MW=3374.5, Storage: -20°C
Sequence from Ca2+/calmodulin-dependent kinase A subunit negative regulatory sequence containing the calmodulin binding site (290-309) plus autophosphorylation site (Thr-286)145,146. Peptide can be phosphorylated at Thr-286 by PKC147. Useful as a CaM binding peptide and inhibits CaMKII by blocking Ca2+/CaM activation and the enzyme active-site. IC50=80 nM, CaM binding; IC50=2 µM, active-site148.
0.5 mg
5 x 0.5 mg

P-202
CaM kinase II [Ala-286](281-302), inhibitor
Met-His-Arg-Gln-Glu-Ala-Val-Asp-Cys-Leu-Lys-Lys-Phe-Asn-Ala-Arg-Arg-Lys-Leu-Lys-Gly-Ala
>97%, MW=2600.2, Storage: -20°C
Sequence is from Ca2+/calmodulin-dependent protein kinase II autophosphorylation site within the pseudosubstrate negative regulatory region149. Inhibition of CaMKII is as effective as 281-309 (IC50=2 µM) but kinetics are not complicated by phosphorylation of the peptide by CaMKII itself (Thr to Ala-286)98,148.
0.5 mg
5 x 0.5 mg

P-211
AIP, CaM kinase II inhibitory peptide
>97%, MW=1498.0, Storage: -20°C
AIP (autocamtide-2-related inhibitory peptide) is a highly-specific and potent inhibitor of CaM kinase II. This peptide is derived from the CaM kinase II substrate autocamtide-2 (BIOMOL catalog #P-101) but alanine is substituted for threonine at the 9-position. AIP at 1 µM completely inhibited CaM kinase II but did not affect PKC, PKA, CaMKIV and other brain extract kinases150,151.
1 mg
5 x 1 mg

P-212
Myristoylated-AIP, CaM kinase II inhibitor
>97%, MW=1708.0, Storage: -20°C
This peptide is the same as AIP (P-211 above) but is N-terminal myristoylated to increase cell-permeability. This inhibitory peptide may be highly useful in cellular studies.
0.5 mg
5 x 0.5 mg

CaMKII ANTIBODY

SA-162
Anti-Ca2+/calmodulin kinase II, a-subunit (CaMKIIa)
Mouse monoclonal antibody. Clone 6G9. Immunogen: Partially purified CaMKII152. Supplied as purified IgG1, lyophilized. Recognizes 50 kDa a-subunit of CaMKII in all mammalian cells plus chick and frog153,154. Reacts with the phosphorylated and non-phosphorylated forms. Applications: WB 10 µg/ml, IC 10 µg/ml.
100 µg

MYOSIN LIGHT CHAIN KINASE (MLCK)

MLCK SUBSTRATES

P-114
MLCK substrate, skeletal and smooth muscle
Lys-Lys-Arg-Ala-Ala-Arg-Ala-Thr-Ser-Asn-Val-Phe-Ala-NH2
>97%, MW=1418.8, Storage: -20°C
Sequence is chicken gizzard smooth muscle myosin P-light chain (MLC 11-23) with Pro to Ala-14 and Gln to Ala-15 substitutions. Contains specificity determinants for MLC phosphorylation (target is Ser-19) and is an excellent myosin light chain kinase (MLCK) substrate. Km=8.6 µM for rabbit skeletal muscle MLCK, 7.5 µM for chicken gizzard smooth muscle MLCK11,155-157.
1 mg
5 x 1 mg

P-115
MLCK substrate, skeletal muscle
Ala-Lys-Arg-Pro-Gln-Arg-Ala-Thr-Ser-Asn-Val-Phe-Ser-NH2
>97%, MW=1460.8, Storage: -20°C
Sequence is chicken gizzard smooth muscle myosin P-light chain (MLC 11-23) with Lys to Ala-11 substitution. Myosin light chain kinase (MLCK) substrate similar to Ala-14,15 peptide but this has slightly higher Kmand lower Vmax. Km=13.3 µM for rabbit skeletal muscle MLCK157.
1 mg
5 x 1 mg

MLCK INHIBITORS

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES)

EI-197
ML-7
1-(5-Iodonaphthalene-1-sulfonyl)-1H-hexahydro-l,4-diazepine·HCl
99%, MW=452.7 [109376-83-2] Storage: 0°C
Potent and selective inhibitor of MLC kinase (Ki=0.3 µM)158. See Table 4 for selectivity data.
10 mg
50 mg

EI-153
ML-9
1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-l,4-diazepine·HCl
99%, MW=361.3 [105637-50-1] Storage: 0°C
Selective inhibitor of MLC kinase (Ki=3.8 µM)158,159. Inhibits insulin-stimulated 2-deoxyglucose transport160 and PP-1 activation161 in adipocytes, possibly via an effect on MAP kinase or its activation160. See Table 4 for selectivity data.
10 mg
50 mg

P-209
MLCK inhibitor
Lys-Arg-Arg-Trp-Lys-Lys-Asn-Phe-Ile-Ala-Val-NH2
>97%, MW=1444.9, Storage: -20°C
Sequence from skeletal muscle myosin light chain kinase (MLCK) (342-352) pseudosubstrate site. Inhibits MLCK (Ki =1 µM with MLC peptide substrate). Possesses only slight calmodulin binding activity162,155.
1 mg
5 x 1 mg


CASEIN KINASE II ENZYME AND REAGENTS

SE-124
Casein kinase II (human, recombinant)
MW=44 and 26 kDa subunits (EC 2.7.1.37) Storage: -70°C
Expressed in E. coli. Supplied in Tris/NaCl/0.1% Triton X-100. Consists of 44 kDa a catalytic and 26 kDa b regulatory subunits as an a2b2 tetramer169. Free from proteases and phosphatases. Supplied at 0.7 mg/ml. Specific activity: 700 kU/mg protein. One unit will transfer 1 pmol phosphate from ATP to peptide substrate per minute at 30°C163.
10 kU
5 x 10 kU

P-113
Casein kinase II peptide substrate
Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu
>97%, MW=1206.3, Storage: -20°C
Sequenced based on CKII phosphorylation sites in casein. Substrate is specific for CKII (Km=0.5 mM), not PKA, PKG, phosphorylase kinase, MLCK, RPTK, or CKI164. Used in phosphocellulose assay with crude extracts of bovine liver165.
1 mg
5 x 1 mg

EI-231
DRB
5,6-Dichloro-1-b-D-ribofuranosylbenzimidazole
98%, MW=319.1 [53-85-0] Storage: -20°C
DRB is a potent and specific inhibitor of casein kinase II (CKII, IC50~6 µM). It has been used to inhibit RNA polymerase II transcription which may be dependent on CKII166 and its interaction with ATF-1167.
10 mg
50 mg

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES

SA-163
Anti-Casein kinase II, a-subunit (CKIIa)
Mouse monoclonal antibody. Clone 1AD9. Immunogen: Recombinant CKIIa168,169. Supplied as purified IgG1, lyophilized. Recognizes p40-44 kDa catalytic a-subunit of CKII. Applications: WB 1-5 µg/ml.
100 µg


MAP KINASE (MAPK)

MAPK ENZYME

SE-137
MAP Kinase, activated (rat, recombinant)
>95% by SDS-PAGE, MW=42 kDa, Storage: -70°C
This is the ERK2 (p42mapk) isoform cloned from a rat skeletal muscle cDNA library. It is constructed with a 6-His N-terminal tag to facilitate purification, and expressed in E. coli. The enzyme was then activated by phosphorylation in vitro using a constitutively active MEK1 mutant. The MAP kinase was repurified and contains no contaminating MEK1 as detected by SDS-PAGE and Western blotting. Supplied at 0.1 mg/ml. Specific activity: ~2 µmol phosphate/min/mg at 30°C using myelin basic protein (MBP) as substrate. Useful to study enzyme regulation, kinetics, and phosphorylate target substrates170-172.
5 µg
5 x 5 µg

SE-139
MAP Kinase, nonactivated (rat, recombinant)
>95% by SDS-PAGE, MW=42 kDa, Storage: -70°C
Identical to SE-137 above, but not activated by MEK1. Supplied at 0.5 mg/ml. Specific activity: ~2 nmol phosphate/min/mg at 30°C using myelin basic protein (MBP) as substrate. Potential activation by MEK1 is 1000-fold. Useful to study enzyme activation by other kinases and as a control for activated MAP kinase (SE-137).
20 µg
5 x 20 µg


MAPK SUBSTRATES

P-121
EGF-R (661-681) T669 Peptide, MAP Kinase Substrate
Lys-Arg-Glu-Leu-Val-Glu-Pro-Leu-Thr-Pro-Ser-Gly-Glu-Ala-Pro-Asn-Gln-Ala-Leu-Leu-Arg
>97%, MW=2315.0 Storage: -20°C
Peptide sequence is based on the cytoplasmic domain of the EGF-receptor, inclusive of Thr-669, a major phosphorylation site in cells stimulated by IL-1, PMA and EGF173,174. This is an excellent substrate for MAP kinase but a poor substrate for MAPKK175.
1 mg
5 x 1 mg

P-122
MBP (95-98) S5 Peptide, MAP Kinase Substrate
Ala-Pro-Arg-Thr-Pro-Gly-Gly-Arg-Arg
>97%, MW=967.0, Storage: -20°C
Peptide sequence is based on myelin basic protein (MBP) residues 95-98 inclusive of Thr-97, the major site of phosphorylation by MAP kinase in vitro176-178.
1 mg
5 x 1 mg

P-124
Erk1/Erk2 Peptide, MAP kinase kinase substrate
Ala-Asp-Pro-Asp-His-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-Trp-Arg-Arg
>97%, MW=2543.8, Storage: -20°C
Sequence is based on Erk1/Erk2 residues 172-190 MAP kinase kinase phosphorylation site (underlined)179. N-terminal Arg is added for phosphocellulose binding180.
1 mg
5 x 1 mg


MAPK ANTISENSE OLIGO'S

ZA-100
MAP Kinase Antisense Oligo
>90% by HPLC and capillary electrophoresis, MW=5.2 kDa, Storage: -70°C.
This is a 17-mer phosphorothioate oligodeoxynucleotide. It is directed against a sequence which is identical in the p42 and p44 MAP kinase isoforms (ERK2, ERK1) and conserved in human, mouse and rat. When complexed with the cationic lipid DOTMA and applied at 2 µM, it eliminated immunodetectable p42 and p44 MAP kinases from 3T3 L1 fibroblasts in 48 hrs.181. Differentiation of the fibroblasts into adipocytes was blocked at > 1 µM181. It depleted MAP kinase >90% in rat aortic smooth muscle cells (DOTAP complex, 5-10 µM)182. A 10 µM treatment of these cells eliminated angiotensin II or PDGF-stimulated MAP kinase activity and reduced PDGF-stimulated DNA synthesis by 95%. There was no effect on expression of the MAP kinase homologs, p38 and JNK, and no effect on MEK activation182. Supplied lyophilized.
25 nmols

ZA-101
MAP Kinase Control Oligo
>90% by HPLC and capillary electrophoresis, MW=5.2 kDa, Storage: -70°C.
Phosphorothioate 17-mer oligodeoxynucleotide with the same base composition as the MAP kinase antisense oligonucleotide ZA-100 above, but is a randomized sequence. Does not affect MAP kinase expression or activity181,182. Supplied lyophilized.
25 nmols

ZP-100
MAP Kinase Antisense and Control Oligo Pair
Twenty-five nanomoles each of ZA-100 and ZA-101, above.
1 pair

MAPK INHIBITORS

(SEE TABLE 4 FOR SER/THR KINASE INHIBITOR SPECIFICITIES)

EI-360

PD-98059
>95%, MW=267.3 [167869-21-8] Storage: -20?/font>C
PD-98059 is a new, potent and selective inhibitor of MAP kinase kinase (MEK). It selectively blocks the activation of MEK thereby inhibiting the phosphorylation and the activation of MAP kinase183,184. PD-98059 is cell permeable. In PC12 pheochromocytoma cells, it completely blocked the increase in MAP kinase activity produced by NGF, IC50=2 mM183,185. PD-98059 is an invaluable, new tool to help elucidate the role of the MAPK cascade in a variety of biological systems.
5 mg
5 x 5 mg

JUN KINASE

SE-150
C-JUN N-terminal kinase (rat, recombinant)
>95% by SDS-PAGE, MW=52 kDa, Storage: -70°C
This c-jun kinase (JNK3, SAPK-b, p54b) was cloned from a rat skeletal muscle cDNA library and expressed in E. coli186. The expression vector encoded a fusion protein comprising (from N- to C-terminus): A calmodulin binding peptide (rat MLCK residues 579-605), thrombin cleavage site, and JNK3 (MW=48.1 kDa). The recombinant protein was purified by affinity chromatography on a calmodulin resin. Supplied at 0.4 mg/ml. Specific activity: 40 nmol phosphate/min/mg at 30°C using GST-c-jun (1-79) fragment (catalog #SE-151, below) as substrate. Useful to study enzyme regulation, kinetics, and phosphorylate target substrates.
20 µg
5 x 20 µg

SE-151
C-JUN (1-79), c-jun kinase substrate (rat, recombinant)
>95% by SDS-PAGE, MW=37 kDa, Storage: -70°C
This is a GST-fusion protein of the c-jun (1-79) activation domain, expressed in E. coli. It is a highly specific substrate for JNK/SAPK It is not appreciably phosphorylated by MAP kinase or by p38 kinase. It can be used as a substrate for c-jun kinase (catalog SE-150, above) at 2 µg per assay187,188. Supplied at 1 mg/ml.
250 µg
5 x 250 µg


SER/THR KINASES - BROAD SPECIFICITY INHIBITORS

EI-145
A-3
N-(2-Aminoethyl)-5-chloronaphthalene-1-sulfonamide·HCl
98%, MW=321.23, Storage: 0°C
Inhibits PKA (Ki=4.3 µM), PKG (Ki= 3.8 µM), MLCK (Ki=7.4 µM) and PKC (Ki=47 µM)189. See Table 4.
10 mg
50 mg

EI-148
H-7
1-(5-Isoquinolinesulfonyl)-2-methylpiperazine?HCl
99%, MW=364.3 [84477-87-2] Storage: 0°C
Inhibits PKA (Ki=3.0 µM), PKG (Ki=5.8 µM), MLCK (Ki=97 µM) and PKC (Ki=6 µM)190. See Table 4.
10 mg
50 mg

EI-195
H-9
N-(2-Aminoethyl)-5-isoquinolinesulfonamide?HCl
99%, MW=324.3 [84468-17-7] Storage: 0°C
H-9 is an excellent affinity ligand for chromatographic purification of protein kinases191,192. It also inhibits protein kinases190. See Table 4 for selectivity data.
10 mg
50 mg

EI-152
K-252a
99%, MW=467.5 [97161-97-2] Storage: 0°C
Inhibits PKA (Ki=0.018 µM), PKG (Ki=0.020 µM), MLCK (Ki=0.017 µM), PKC (Ki=0.025 µM)193,194, CaMK (Ki=0.0018 µM)195 and phosphorylase kinase (IC50=1.7 nM)196. See Table 4. Potent inhibitor of the trk family of receptor tyrosine kinases197,198,199 and MAP kinase200.
100 µg
1 mg

EI-234
K-252b
99%, MW=453.5 [99570-78-2] Storage: 0°C
Inhibits PKA (Ki=0.09 µM), PKG (Ki=0.1 µM), MLCK (Ki=0.147 µM) and PKC (Ki=0.02 µM)193. See Table 4.
100 µg
1 mg

EI-156
Staurosporin
99%, MW=466.5 [62996-74-1] Storage: 0°C
Staurosporin inhibits a variety of kinases including PKA (Ki=7.0 nM), PKG (Ki=8.5 nM), MLCK (Ki=1.3 nM), PKC (Ki=0.7 nM)201,202, CaMK (IC50=20 nM)203, tyrosine kinases (IC50=70 nM)204,205 and phosphorylase kinase (IC50=0.5 nM)196. See Table 4. Inhibition is via interaction with the ATP binding site206. It induces PKC translocation207 and augments PMA induced ornithine decarboxylase208. Activates a bcl-2-regulated apoptosis pathway209.
100 µg
1 mg
NEW LOWER PRICE

TABLE 4. SPECIFICITIES OF SELECTED SER/THR KINASE INHIBITORS.

[Inhibition as Ki or (IC50), concentration in µM]

Kinase

PKA

PKC

PKG

MLCK

CaMKII

CK-I

CK-II

Inhibitor

             
A-3

4.3

47

3.8

7.4

  80

5.1

Calphostin C

(>50)

(0.05)

(>25)

(>5)

     
Chelerythrine

(170)

(0.66)

    (>100)

   
GF 109203X

(2)

(0.02)

         
H-7

3.0

6.0

5.8

97

     
H-8

1.2

15

0.48

68

     
H-9

1.9

18

0.87

70

     
H-89

0.048

31.7

0.48

28.3

29.7

38.3

137

HA-1004

2.3

40

1.3

150

     
HA-1077

1.6

  1.6

36

     
Hypericin

(>79)

(3.4)

  (>40)

     
K-252a

0.018

0.025

0.020

0.017

0.0018

   
K- 252b

0.09

0.02

0.1

0.147

     
KN-62

>100

>100

  >100

0.9

   
KT5720

0.056

>2

>2

>2

     
KT5823

>10

4

0.234

>10

     
KT5926

1.2

0.723

0.158

0.018

0.0044

   
ML-7

21

42

  0.3

     
ML-9

32

54

  3.8

     
Staurosporin

0.007

0.0007

0.0085

0.0013

(0.02)

   


Abbreviations used are: PKA, cAMP-dependent protein kinase; PKC, protein kinase C; PKG, cGMP-dependent protein kinase; MLCK, myosin light-chain kinase; CaMKII, Ca2+/calmodulin kinase II; CK-I, casein kinase I; CK-II, casein kinase II.


SER/THR KINASES - MISCELLANEOUS REAGENTS

P-116
S6 peptide, protein kinase substrate
Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala
>97%, MW=958.2, Storage: -20°C
Sequence is from rat hepatic 40S ribosomal protein S6 (232-239). Substrate for p90 rsk (S6K) in cell extracts (Km=0.18 mM) using phosphocellulose assay. Peptide phosphorylation by PKA and PKC can be eliminated by the inclusion of PKI and EGTA, respectively, in the assay210-212.
1 mg
5 x 1 mg

ST-101
Adenosine-5'-O-(3-thiotriphosphate)·Li4 (ATPg-S)
>85%, MW=547.0 [93839-89-5] Storage: -20°C
An ATP analog that can substitute for ATP in various kinase reactions. The resulting thiophosphorylated proteins are resistant to dephosphorylation by protein phosphatases213.
5 mg
25 mg

ST-102
Anisomycin
97%, MW=265.3 [22862-76-6] Storage: -20°C
Activates JNK/SAPKs but not ERKs leading to the phosphorylation of S6, histone H3 and HMG-14 and the induction of the immediate-early genes c-fos and c-jun214-216.
10 mg
50 mg

EI-144
Mezerein
99%, MW=654.7 [34807-41-5] Storage: -20°C
A non-phorbol ester diterpene comparable to PMA as an inflammatory agent but less potent as a tumor promotor217. A potent "second stage" tumor promotor218.
1 mg
5 mg


TYROSINE KINASES

A great deal of attention is currently being focused on the role of tyrosine kinases219 in receptor-mediated signal transduction220,221. Several oncogene products219,222 as well as a number of receptors for growth factors including EGF223, PDGF224, NGF225 and insulin226 are tyrosine kinases. In platelets, both PAF227 and a thromboxane A2 agonist228 were found to stimulate tyrosine phosphorylation as were thrombin229 and collagen230. In human neutrophils, the chemotactic factor fMLP and GM-CSF both induced tyrosine phosphorylation of several proteins231. In lymphocytes including T cells232,233, B cells234 and NK cells235, tyrosine phosphorylation was shown to be an early, critical event in receptor mediated activation.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)

EGFR ENZYME

SE-167
EGF Receptor Kinase Domain, protein tyrosine kinase (human, recombinant)
Inquire

SE-116
EGF Receptor, protein tyrosine kinase (from human A431 cells)
>90% by SDS-PAGE, MW=170 kDa, Storage: -70°C
Supplied in 10% glycerol, 0.05% Triton X-100 buffer containing 5 mM EGF. EGFR is active but not autophosphorylated. Specific activity: 45 U/ml. One unit will add one pmol phosphate to angiotensin II per minute at pH 7.4 and 30°C.
10 U


EGFR INHIBITORS

(SEE TABLE 5 FOR TYROSINE KINASE INHIBITOR SPECIFICITIES)

EI-228
AG-494
99%, MW=280.3, Storage: RT
AG-494 is a member of the tyrphostin family of tyrosine kinase inhibitors and is a potent inhibitor of EGF receptor autophosphorylation (IC50=1.2 µM) and EGF-dependent cell growth (IC50=6 µM)236. It selectively inhibits HER1 (EGF receptor) vs. HER1-2 receptor autophosphorylation. HER1: IC50=1.1 µM; HER1-2: IC50=45 µM237. HER1-2 is a chimeric receptor consisting of the external HER1 domain fused to an internal HER2 domain. See Table 5 for selectivity data.
10 mg
50 mg

EI-267
AG-825
5-[(Benzthiazol-2-yl)thiomethyl]-4-hydroxy-3-methoxybenzylidenecyanoacetamide
98%, MW=397.5, Storage: RT
A selective HER1-2 (HER2-Neu)238 tyrosine kinase inhibitor237. See Table 5 for selectivity data.
2 mg
10 mg

EI-277
AG-1478
4-(3-Chloroanilino)-6,7-dimethoxyquinazoline
>98%, MW=315.8 [63177-57-1] Storage: -20°C
Potent and selective inhibitor of EGFR (IC50=3 nM)238. It reduces EGF-stimulated DNA synthesis in Rat-1 fibroblasts by ~75% at 0.25 µM239. Blocks EGF-dependent src-family kinase activation240 and p21/Cip1/WAF1 induction241 in A431 cells. Also inhibits H2O2 -induced stimulation of amphiregulin expression in rat gastric epithelium (RGM 1) cells242. See Table 5 for selectivity data.
5 mg
25 mg

EI-146
Erbstatin Analog
Methyl 2,5-dihydroxycinnamate
98%, MW=194.0 [63177-57-1] Storage: RT
Erbstatin is a novel inhibitor of the EGF receptor associated tyrosine kinase243. It is an unstable compound and is completely inactivated in serum in 30 minutes. Methyl 2,5-dihydroxycinnamate is a stable erbstatin analog retaining activity after a 60 minute incubation. It inhibits EGF receptor associated tyrosine kinase in vitro (IC50=0.77 µM)244. Inhibition is competitive with substrate and noncompetitive with ATP.
5 mg
25 mg

EI-232
HDBA
2-Hydroxy-5-(2,5-dihydroxybenzylamino)benzoic acid
Inhibits EGF receptor tyrosine kinase (IC50=0.044 µM)136 and pp60c-src(+) kinase (IC50=0.5 µM)135. Also inhibits Ca2+/calmodulin kinase II (IC50=0.2 µM)135.

EI-185
Lavendustin A
98%, MW=381.4 [125697-92-9] Storage: 0°C
Lavendustin A is a potent and selective inhibitor of the EGF receptor tyrosine kinase (IC50=11 nM) It binds to a site on the kinase which is distinct from the ATPand peptide substrate binding sites246. Inhibited EGF-induced proliferation of cultured human myometrial smooth muscle cells247. Suppressed VEGF-induced angiogenesis in rats248. See Table 5 for selectivity data.
1 mg
5 mg

EI-252
RG-13022
99%, MW=266.3 [136831-48-6] Storage: RT
RG-13022 is a non-phenolic tyrphostin analog which inhibits the EGF receptor (IC50=5 µM) and PDGF receptor tyrosine kinases and is long acting. It inhibits EGF-stimulated HER14 cell proliferation (IC50=1 µM) as well as tumor growth in vivo249. It inhibits both EGF- and PDGF-stimulated DNA synthesis in human glioma cell lines. RG-13022 is non-phenolic and therefore possesses less antioxidant activity than other tyrphostins.
5 mg
25 mg

EI-253
RG-14620
99%, MW=274.1 [136831-49-7] Storage: RT
RG-14620 is a non-phenolic tyrphostin analog which is selective for the EGF receptor and long acting. It inhibits EGF-stimulated HER14 cell proliferation (IC50=3 µM) as well as tumor growth in vivo249. Has anti-proliferative effects on renal and bladder carcinoma cell lines251.
5 mg
25 mg

EI-191
Tyrphostin 23 (RG-50810)
99%, MW=186.1 [118409-57-7] Storage: RT
A potent inhibitor of EGF receptor kinase activity252,253,257. See Table 5 for selectivity data.
10 mg
50 mg

EI-187
Tyrphostin 25 (RG-50875)
99%, MW=202.1 [118409-58-8] Storage: RT
A potent inhibitor of EGF receptor kinase activity253,257,296. See Table 5 for selectivity data.
5 mg
25 mg

EI-257
Tyrphostin 46
99%, MW=204.2 [122520-85-8] Storage: RT
Inhibits EGF receptor kinase286, p56lck254 and PDGF255 receptor kinase. See Table 5 for data.
10 mg
50 mg

EI-188
Tyrphostin 47 (RG-50864, AG-213)
99%, MW=220.2 [122520-86-9] Storage: RT
A potent inhibitor of EGF receptor kinase activity252,253,257. See Table 5 for selectivity data.
5 mg
25 mg

EI-189
Tyrphostin 51
99%, MW=268.2 [122520-90-5] Storage: 0°C
A potent inhibitor of EGF receptor kinase activity. Inhibition is mixed competitive with ATP and substrate253,256,257. See Table 5 for selectivity data.
5 mg
25 mg

EI-190
Tyrphostin 1
99%, MW=184.2 [2826-26-8] Storage: RT
An inactive tyrphostin which may be used as a negative control257. See Table 5.
20 mg
100 mg

EGFR ANTIBODIES

SA-110
Anti-Epidermal growth factor receptor (EGFR)
Mouse monoclonal antibody. Clone EGFR1. Immunogen: Whole A431 human epidermal carcinoma cells258. Supplied as purified IgG2b, 0.1 mg/ml. Reacts with human EGFR 175 kDa extracellular domain. Does not inhibit EGF binding. Applications: WB, IP, IF.
200 µg

SA-111
Anti-Epidermal growth factor receptor (EGFR)
Mouse monoclonal antibody. Clone F4. Immunogen: Human EGFR (985-996) peptide259. Supplied as purified IgG1, 0.1 mg/ml. Reacts with 170 kDa EGFR intracellular domain. Recognizes autophosphorylated EGFR and the related v-erb B protein, but the immunoprecipitated EGFR can not autophosphorylate. Applications: IP, IF, IH, ELISA.
200 µg

INSULIN RECEPTOR

The insulin receptor is a tyrosine kinase that is present in virtually all vertebrate tissues. It is composed of two a-subunits that are each linked to a b-subunit and to each other by disulfide bonds. The a-subunits are located extracellularly and contain the insulin binding site, whereas the intracellular portion of the b-subunit contains the protein tyrosine kinase domain. Regulatory autophosphoryation sites in the b-subunit consists of Tyr 1146, 1150, and 1151. Autophosphorylation of all 3 tyrosine residues in the YXXXYY motif of this region stimulates kinase activity 10- to 20-fold260. The following phosphopeptides correspond to the insulin receptor regulatory region. These peptides can be used to study insulin receptor signalling. In addition, they have been used as tyrosine phosphatase substrates in non-radioactive PTPase assays261.

INSULIN RECEPTOR ENZYME

SE-159
b-Insulin Receptor Kinase (b-IRK), protein tyrosine kinase (human, recombinant)
48 kDa cytoplasmic domain of the b-subunit (resudues 941-1343), expressed in a baculovirus expression system.
Inquire



INSULIN RECEPTOR SUBSTRATES

P-314
IR0, Insulin Receptor [1142-1153]
Thr-Arg-Asp-Ile-Tyr-Glu-Thr-Asp-Tyr-Tyr-Arg-Lys
>97%, MW=1622.9, Storage: -20°C
Sequence is from insulin receptor b-subunit cytoplasmic domain, inclusive of regulatory autophosphorylation sites Tyr 1146, 1150 and 1151260. It has been used as an insulin receptor tyrosine kinase substrate262,261 and the phosphorylated peptide as a protein tyrosine phosphatase substrate.
0.5 mg
5 x 0.5 mg

P-315
IR5, Insulin Receptor [1142-1153] (pY1146)
Thr-Arg-Asp-Ile-pTyr-Glu-Thr-Asp-Tyr-Tyr-Arg-Lys
>97%, MW=1703.0, Storage: -20°C
0.5 mg
5 x 0.5 mg

P-316
IR9, Insulin Receptor [1142-1153] (pY1150)
Thr-Arg-Asp-Ile-Tyr-Glu-Thr-Asp-pTyr-Tyr-Arg-Lys
>97%, MW=1703.0, Storage: -20°C
0.5 mg
5 x 0.5 mg

P-317
IR10, Insulin Receptor [1142-1153] (pY1151)
Thr-Arg-Asp-Ile-Tyr-Glu-Thr-Asp-Tyr-pTyr-Arg-Lys
>97%, MW=1703.0, Storage: -20°C
0.5 mg
5 x 0.5 mg

P-318
IR5,9,10, Insulin Receptor [1142-1153] (pY1146,1150,1151)
Thr-Arg-Asp-Ile-pTyr-Glu-Thr-Asp-pTyr-pTyr-Arg-Lys
>97%, MW=1863.0, Storage: -20°C
0.5 mg
5 x 0.5 mg

P-319
Insulin Receptor Phosphopeptide Kit
Contains 0.5 mg each of the above peptides: (P-314, P-315, P-316, P-317, P-318)
1 kit

P-320
IRS-1 (Y608) peptide
Lys-Lys-His-Thr-Asp-Asp-Gly-Tyr-Met-Pro-Met-Ser-Pro-Gly-Val-Ala
>97%, MW=1732.8, Storage: -20°C
Sequence is from insulin receptor substrate 1 (IRS-1) inclusive of Tyr-608. It contains the insulin receptor tyrosine kinase substrate motif YMXM (Tyr-Met-X-Met). This peptide has been used as a substrate for purified insulin receptor (Km=90 µM)263 and other tyrosine kinases264 in phosphocellulose binding assays. The tyrosine phosphorylated version of this peptide binds to phosphatidylinositol 3-kinase (PI 3-kinase) SH2 domain and activates the enzyme265.
1 mg
5 x 1 mg

INSULIN RECEPTOR INHIBITORS

(SEE TABLE 5 FOR TYROSINE KINASE INHIBITOR SPECIFICITIES)

EI-247
HNMPA
Hydroxy-2-naphthalenylmethylphosphonic acid
98%, MW=238.2, Storage: -20°C
HNMPA is a membrane impermeable inhibitor of insulin receptor tyrosine kinase activity (IC50=100 µM)266. It was recently shown to inhibit both tyrosine and serine autophosphorylation by the human insulin receptor267.
5 mg
25 mg

EI-248
HNMPA-(AM)3
Hydroxy-2-naphthalenylmethylphosphonic acid-tris acetoxymethylester
98%, MW=454.4, Storage: -20°C
HNMPA-(AM)3 is a cell permeable analog of HNMPA. It inhibits insulin receptor tyrosine kinase activity (IC50=100 µM) and insulin-stimulated glucose oxidation in isolated rat adipocytes (IC50=10 µM). It has no effect on PKA (at concs. up to 1 mM) or PKC (at concs. up to 420 µM)266.
5 mg
25 mg


SRC-FAMILY

SRC-FAMILY INHIBITORS

(SEE TABLE 5 FOR TYROSINE KINASE INHIBITOR SPECIFICITIES)

EI-274
Damnacanthal
95%, MW=282.3 [477-84-9] Storage: -20?/font>C
Damnacanthal is the most potent and selective inhibitor of p56lck tyrosine kinase described to date268. It inhibits p56lck autophosphorylation (IC50=17 nM) as well as phosphorylation of exogenous substrates (IC50=620 nM) in cell-free assays. Damnacanthal shows a >10-fold selectivity for p56lck over PKA and PKC and >40-fold selectivity over four receptor tyrosine kinases as well as 7-20-fold selectivity over the homologous enzymes p60src and p59fyn. Damnacanthol is not active in whole cell tyrosine kinase assays.
1 mg
5 x 1 mg

EI-227
Herbimycin A
98%, MW=574.3 [70563-58-5] Storage: -20°C
Herbimycin A, a benzoquinoid ansamycin antibiotic, irreversibly and selectively inhibits tyrosine kinases by reacting with thiol groups269,270. It is effective on Src, Yes, Fps, Ros, Abl and ErbB oncogene products269,270,271 and inhibits thrombin-induced tyrosine phosphorylation of phospholipase C272.
100 µg
1 mg

EI-271
Piceatannol
3,4,3',5'-Tetrahydroxy-trans-stilbene
98%, MW=244.3 [10083-24-6] Storage -20?/font>C
Piceatannol preferentially inhibits the activity of Syk (IC50~10 mM) as compared with Lyn in isolated enzyme preparations. In RBL-2H3 cells the selective inhibition of Syk by piceatannol results in inhibition of FceR1-mediated signaling273.
1 mg
5 x 1 mg

EI-275
PP1
98%, MW=281.4, Storage: -20?/font>C
A highly potent and selective inhibitor of Src family tyrosine kinases, IC50=5 nM for p56lck; p59lyn=6 nM; p60src=170 nM. Inhibition of T-cell phosphorylation in response to anti-CD3 activation occurs at 10 µM274.
1 mg
5 mg


SRC-FAMILY PEPTIDES

P-307
pp60v-src autophosphorylation site, protein tyrosine kinase substrate
Arg-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-Arg-Gly
>97%, MW=1592.9 [81493-98-3] Storage: -20°C
Residues 2-12 are the v-src (412-422) autophosphorylation site with an extra Arg for phosphocellulose binding. This substrate was originally described as an EGF-receptor substrate in A431 cell extracts (Km=0.3-0.6 mM)275.
1 mg
5 x 1 mg

P-312
pp60v-src autophosphorylation site, tyrosine phosphopeptide
Arg-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(PO3H2)-Thr-Ala-Arg-Gly
>97%, MW=1671.9, Storage: -20°C
Same as P-307 but this peptide is tyrosine phosphorylated. Useful in a non-radiolabeled tyrosine phosphatase assay and as a competitive tyrosine phosphatase inhibitor.
1 mg
5 x 1 mg

P-308
RR-SRC, protein tyrosine kinase substrate
Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly
>97%, MW=1519.9 [81156-93-6] Storage: -20°C
Tyrosine kinase substrate derived from v-src autophosphorylation site (original src sequence is IEDNEYTARQG). Km=5 mM in LSTRA cell extracts276.
1 mg
5 x 1 mg

P-306
Peptide A, protein tyrosine kinase inhibitor
Val-Ala-Pro-Ser-Asp-Ser-Ile-Gln-Ala-Glu-Glu-Trp-Tyr-Phe-Gly-Lys-Ile-Thr-Arg-Arg-Glu
>97%, MW=2482.8, Storage: -20°C
Sequence is pp60v-src (137-157) which is located in the SH3/SH2 domain region277. Non-competitive inhibitor of src and EGF-R278. Selectively inhibits protein tyrosine phosphorylation in cell extracts. Peptide is not phosphorylated by src. IC50=7.5 µM for v-src. Inhibitory target seems to be a catalytic negative regulatory domain of the tyrosine kinase279.
0.5 mg
5 x 0.5 mg


SRC-FAMILY ANTIBODIES

SA-137
Anti-Src, human endogenous
Rabbit polyclonal antibody. Immunogen: Rous sarcoma virus (RSV). Supplied as serum. Specificity: pp60c-src from human, rat, mouse and chick plus other viral proteins of RSV. Can detect src in fibroblasts, endothelial and neuronal cells. Applications: WB 1/1000, IF 1/100, IP.
200 µl

SA-248
Anti-Syk
Mouse monoclonal antibody. Clone 4D10.1. Immunogen: Human Syk (313-339) peptide conjugated to KLH. Supplied as purified IgG2a, 0.2 mg/ml. Recognizes 72 kDa human syk tyrosine kinase. Does not crossreact with pig or mouse. Applications: WB 1 µg/ml, IP (active in immune-complex kinase assays), IH.
100 µg


OTHER TYROSINE KINASE INHIBITORS

EI-272
AG-490
98%, MW=294.3 Storage: -20?/font>C
AG-490 is a potent inhibitor of the JAK-2 tyrosine kinase. In acute lymphoblastic leukemia (ALL) cells which abundantly express JAK-2, AG-490 dose-dependently inhibited DNA synthesis, blocked cell growth and induced apoptosis. At 5 mM, AG-490 almost completely blocked the growth of all pre-B ALL cells but had no significant effect on the growth of mitogen-stimulated normal B or T cells, B-cell lymphoma or T-cell leukemia cells. AG-490 does not significantly inhibit other kinases such as Lck, Lyn, Btk, Syk and Src280. It blocks interleukin-7-induced JAK kinase activity in T-cells (JAK-1, JAK-3) and the consequent phosphorylation of PI-3 kinase281,282. AG-490 is cell permeable and is a valuable new tool for studying the cellular role of JAK kinases in signal transduction.
5 mg
25 mg

EI-263
AG-126
98%, MW=215.2 Storage: RT
AG-126 prevents lipopolysaccharide-induced lethal toxicity (septic shock) in mice. Administered at 1.5 mg/mouse, it reduced LPS-induced lethal toxicity from 95% to 10%. AG-126 greatly reduces LPS-induced tyrosine phosphorylation of p42MAPK in murine peritoneal macrophages at 50 µM. EGFR, Her-2/neu receptor or PDGF-R are not inhibited at 100 µM283. Inhibits tyrosine kinase-dependent B cell receptor signalling284,285.
5 mg
25 mg

EI-229
AG-370
99%, MW=259.3 Storage: 0°C
AG-370 is a member of the tyrphostin family of tyrosine kinase inhibitors and is a selective inhibitor of the PDGF receptor kinase (IC50=20 µM) vs. the EGF receptor kinase286. AG-370 inhibits PDGF-induced mitogenesis in human bone marrow fibroblasts287. See Table 5 for selectivity data.
2 mg
10 mg

EI-258
AG-879
99%, MW=316.5, Storage: -20°C
AG-879, a member of the tyrphostin family of tyrosine kinase inhibitors, inhibits NGF receptor (pp140c-trk) autophosphorylation selectively with no inhibition of EGF or PDGF receptor phosphorylation (IC50=10 µM)288. AG-879 inhibits NGF-induced neurite outgrowth in PC12 cells288. See Table 5 for selectivity data.
5 mg
25 mg

EI-147
Genistein
4',5,7-Trihydroxyisoflavone
98%, MW=270.2 [446-72-0] Storage: RT
Genistein inhibits tyrosine phosphorylation in isolated enzyme and receptor preparations and in whole cells including platelets227,228, lymphocytes232,233,234 and a variety of cultured cells289-292. In cultured A431 epidermoid carcinoma cells, EGF stimulated tyrosine phosphorylation was totally inhibited by genistein at 100 µg/ml292. Inhibition is competitive with ATP and noncompetitive with substrate (see Table 5 for selectivity).
20 mg
100 mg

ST-110
Daidzein
4',7-Dihydroxyisoflavone
98%, MW=254.2 [486-66-8] Storage: RT
Inactive negative control compound for genistein292. Shares with genistein, a number of effects thought to be unrelated to tyrosine kinase inhibition. These include activation of the human estrogen receptor293, induction of differentiation in leukemia cells294 and inhibition of fast Na+ channels295.
20 mg
100 mg

EI-215
Tyrphostin 9 (RG-50872, Malonaben, SF 6847)
99%, MW=282.4 [10537-47-0] Storage: RT
Tyrphostin 9 is a selective inhibitor of the PDGF receptor tyrosine kinase (IC50=1.2 µM)286,296. It is also a potent (10 nM) uncoupler of oxidative phosphorylation297. See Table 5 for selectivity data.
50 mg
250 mg


TABLE 5. SELECTIVITY OF TYROSINE PROTEIN KINASE INHIBITORS

Catalog #

Compound

Kinase

IC50(µM)

Substrate

Ref.

EI-229

AG-370

EGFR

820

poly-GAT

286
    PDGFR

20

unspecified

286
EI-228

AG-494

EGFR

0.7
1.2

poly-GAT
autophos.

236
    HER1-2

42

autophos.

298
    PDGFR

6

autophos.

237
    IR

>100

unspecified

237
EI-267

AG-825

HER1-2

0.35

autophos.

237
    EGFR

19

autophos.

237
    PDGFR

40

autophos.

237
    p210Bcr-Abl

75

unspecified

238
    IR

>100

unspecified

238
EI-258

AG-879

Trk (NGFR)

10

autophos.

238
    EGFR

>500

autophos.

238
    PDGFR

>100

autophos.

238
EI-277

AG-1478

EGFR

0.003

unspecified

238
    HER2-Neu

>100

unspecified

238
    PDGFR

>100

unspecified

238
    p210Bcr-Abl

>50

unspecified

238
EI-146

Erbstatin Analog

EGFR

0.8

src peptide

244
EI-147

Genistein

EGFR

2.6
22
1

Autophos.
Histone 2B
Ang. II

292

299
    v-src

26

Casein

292
    c-src

>50

poly-GT

299
    v-abl

39

v5-Ang.II

299
    PKA

>100

Histone 2A

292
    PKC

15
>100

Histone H1

299
292
EI-232

HDBA

EGFR

0.011

src peptide

136
    c-src

0.5

poly-GT

135
    CaMK

0.2

  135
EI-247

HNMPA

IR

100

   
EI-185

Lavendustin A

EGFR

0.011

src peptide

245
    PKA

>100

unspecified

245
    PKC

>100

unspecified

245
EI-190

Tyrphostin 1

EGFR

>1250

poly-GAT

257
EI-215

Tyrphostin 9

EGFR

460

poly-GAT

286
  (RG-50872)

PDGFR

0.5

unspecified

286
EI-191

Tyrphostin 23

EGFR

35

poly-GAT

257
  (RG-50810)

  42

Ang. II

299
    PDGFR

20-30

unspecified

286
    IR

1200(Ki)

poly-GT

253
    PKA

>1000

unspecified

253
    PKC

>1000

unspecified

253
EI-187

Tyrphostin 25

EGFR

3
15

poly-GAT
Autophos.

257
253
EI-257

Tyrphostin 46

EGFR

9.2

unspecified

286
    p56lck

22

enolase

254
    PDGF

50

unspecified

255
EI-188

Tyrphostin 47

EGFR

2.4

poly-GAT

257
  (RG-50864)

IR

640(Ki)

poly-GT

253
    PDGFR

3.5

unspecified

286
    Trk

>100

unspecified

238
    p210Bcr-Abl

6

unspecified

238
EI-189

Tyrphostin 51

EGFR

0.8

poly-GAT

257

Abbreviations used are: EGFR, epidermal growth factor receptor; IR, insulin receptor; PDGFR, platelet-derived growth factor receptor; PKA, cAMP-dependent protein kinase; PKC, protein kinase C; Autophos., autophosphorylation; Ang.II, angiotensin II; V5-Ang.II [Val5]angiotensin II; poly-GAT, Glu-Ala-Tyr (6:3:1) polymer; poly-GT, Glu-Tyr (4:1) polymer; src peptide, src autophosphorylation site peptide.

ANTI-PHOSPHOTYROSINE ANTIBODIES

SA-240
PY20, Anti-Phosphotyrosine, mouse monoclonal antibody
Mouse monoclonal antibody. Clone PY20. Immunogen: Phosphotyrosine conjugated to KLH300,301. Supplied as purified IgG2b, 0.1 mg/ml. Recognizes phosphotyrosine in proteins (species independent) and as the free amino acid. No cross-reactivity with phosphoserine or phosphothreonine. This classic anti-phosphotyrosine antibody is now available in convenient package sizes at low cost. High concentrations of salt (>0.2 M) and divalent cations (>1 mM) may inhibit antibody interaction. Applications: WB 1 µg/ml, IC, IH and IP.
25 µg
5 x 25 µg

SA-241
PY20, Agarose Beads
Anti-phosphotyrosine, clone PY20, covalently coupled to 4% cross-linked agarose beads. This product is optimized for binding of phosphotyrosine containing proteins with minimal non-specific binding. Supplied as a 50% slurry (1 ml total volume) at a conjugation ratio of 8-10 mg of PY20 per ml of packed beads. Application: Immunoprecipitation. Storage: 4°C
0.5 ml
5 x 0.5 ml

SA-242
PY20, Fluorescein Conjugate
Anti-phosphotyrosine, clone PY20, conjugated to fluorescein. Supplied at 0.1 mg/ml IgG2b, at a fluorescein/antibody molar ratio of ~4. Application: Immunofluorescence. Storage: 4°C
100 µl

SA-243
PY20, Biotin Conjugate
Anti-phosphotyrosine, clone PY20, conjugated to biotin. Supplied at 0.1 mg/ml IgG2b. Applications: IH, IC. Storage: 4°C
100 µg

SA-154
Anti-Phosphotyrosine
Rabbit polyclonal antibody. Immunogen: Phosphotyrosine conjugated to KLH. Supplied as IgG, affinity purified against immobilized phosphotyrosine. Applications: WB 1-5 µg/ml, ELISA.
100 µg

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