Protein Kinase C (PKC) Interactive Pathway

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Protein Kinase C: Technical Overview
Protein kinase C (PKC), a ubiquitous, phospholipid-dependent enzyme, is involved in signal transduction associated with cell proliferation, differentiation, and apoptosis. At least eleven closely related PKC isozymes have been reported that differ in their structure, biochemical properties, tissue distribution, subcellular localization, and substrate specificity. They are classified as conventional (a, b1, b2, g), novel (d, e, h, q, m), and atypical (z, l) isozymes. Conventional PKC isozymes are Ca2+-dependent, while novel and atypical isozymes do not require Ca2+ for their activation. All PKC isozymes, with the exception of z and l, are activated by diacylglycerol (DAG). PKC isozymes negatively or positively regulate critical cell cycle transitions, including cell cycle entry and exit and the G1 and G2 checkpoints.

In its unstimulated state, most of the PKC resides in the cytosol. In this state, the pseudosubstrate sequence of the regulatory domain of PKC interacts with the catalytic domain and prevents access of the substrate to the catalytic site. Binding of a hormone or other effector molecule to the membrane receptor results in activation of phospholipase C (PLC) or phospholipase A2 (PLA2) via a G-protein-dependent phenomenon. The activated PLC hydrolyzes phosphatidylinositol-4, 5-bisphosphate (PIP2) to produce DAG and inositol-1,4,5-trisphosphate (IP3). The IP3 causes the release of endogenous Ca2+ that binds to the cytosolic PKC and exposes the phospholipid-binding site. The binding of Ca2+ translocates PKC to the membrane, where it interacts with DAG and is transformed into a fully active enzyme.

Altered PKC activity has been linked with various types of malignancies. Higher levels of PKC and differential activation of various PKC isozymes have been reported in breast tumors, adenomatous pituitaries, thyroid cancer tissue, leukemic cells, and lung cancer cells. Down regulation of PKCa is reported in the majority of colon adenocarcinomas and in the early stages of intestinal carcinogenesis. Thus, PKC inhibitors have become important tools in the treatment of cancers. The involvement of PKC in the regulation of apoptosis adds another dimension to the effort to develop drugs that will specifically target PKC.

References:
Mailoi, E., and Fortino, V. 2004. Endocr. Relat. Cancer 11, 161.
Black, J.D. 2000. Front. Biosci. 5, 406.
Cooper, D.R., et al. 1999. Arch. Biochem. Biophys. 372, 69.
Yamamoto, M., et al. 1998. Exp. Cell Res. 240, 349.
Rasmussen, H., et al. 1995. Endocr. Rev. 16, 649.
Taylor, S.S., et al. 1995. FASEB J. 9, 1255.
Nishizuka, Y. 1995. FASEB. J. 9, 484.
Newton, A.C. 1995. J. Biol. Chem. 270, 28495.
Hanks, S., and Hunter, T. 1995. FASEB J. 9, 576.
Blobe, G.C., et al. 1994. Cancer Metastasis Rev. 13, 411.
Basu, A. 1993. Pharmacol. Ther. 59, 257.


Antibodies

Producto Aplicación Reactividad de especies Núm. prod.
Anti-PKCγ (306 - 318) Rabbit pAb ELISA (see comments) Immunoblotting (≥1:500) Immunofluorescence (≥1:500)  bovine, human, rabbit, rat 539529
Anti-PKCα/β (371-388) Rabbit pAb Rabbit pAb ELISA (see comments) Immunoblotting (2 µg/ml, chemiluminescence) Immunoprecipitation (12.5 µg/ml)  <i>Drosophila</i>, <i>Xenopus</i>, bovine, canine, chicken, human, monkey, mouse, ovine, porcine, rabbit, rat 539507
Anti-PKCζ (580-592) Rabbit pAb ELISA (1:1000, see comments)
Immunoblotting (1:200-1:2000, colorimetric)
Immunofluorescence (1:500) 
rat 539538
Anti-PKCδ (658-676) Rabbit pAb Immunoblotting (1:100)  mammalian 539607
Anti-PKCα (662-672) Rabbit pAb Immunoblotting (1-5 µg/ml)  mammalian 539601
Anti-PKCδ (662-673) Rabbit pAb ELISA (see comments)
Immunoblotting (≥1:800) 
rat 539532
Anti-PKCγ (681-697) Rabbit pAb Immunoblotting (1:100, chemiluminescence)  mammalian 539611
Anti-PKCε (721-737) Rabbit pAb Immunoblotting (1:100, chemiluminescence)  mammalian 539609
Anti-PKCε (728-737) Rabbit pAb ELISA (see comments)
Immunoblotting (see comments)
Immunofluorescence (see comments) 
rat 539535
Anti-PKC (Ab-1) Rabbit pAb Immunoblotting (1-5 µg/ml)
Immunofluorescence (1-5 µg/ml) 
chicken, human, mouse PC20
Anti-PKC (Ab-2) Mouse mAb (MC5) Blocking Studies (5 µg/ml, see comments)
Immunoblotting (1 µg/ml)
Immunoprecipitation (see application references)
Paraffin Sections (5 µg/ml, no pre-treatment required) 
bovine, human, mouse, rat OP74
Anti-PKCConsensus (Ac543-550) Rabbit pAb ELISA (1:1000)
Immunoblotting (1:200-500, colorimetric)
Immunocytochemistry (1:500)
Immunoprecipitation (1:100-1000)
Immunofluorescence (1:500) 
bovine, human, mouse, rabbit, rat 539550
Anti-PKCβI (661-671) Rabbit pAb ELISA (1:500) Immunoblotting (1:500) Immunofluorescence (1:500)  rat 539523
Anti-PKCβI (661-671) Rabbit pAb Immunoblotting (1:1000, chemiluminescence)  mammalian 539603
Anti-PKCβII (660-673) Rabbit pAb ELISA (see comments)
Immunoblotting (see comments)
Immunocytochemistry (see comments)
Immunofluorescence (see comments) 
rat 539526
Anti-PKCβII (661-673) Rabbit pAb Immunoblotting (1:100)  mammalian 539605
Anti-PKC (α, β, γ) Mouse mAb (M110) ELISA (1:2000)
Immunoblotting (1:1000)
Immunocytochemistry (1:100)
Immunoprecipitation (5-10 µl) 
human, mouse, rat PK1014

Activators

Producto Núm. prod.
1,2-Dioctanoyl-sn-glycerol - CAS 60514-48-9 - Calbiochem 317505
1-Oleoyl-2-acetyl-sn-glycerol 495414
1-Stearoyl-2-arachidonoyl-sn-glycerol 569399
4α-Phorbol 524382
4α-Phorbol-12,13-didecanoate 524394
α-Amyloid Precursor Protein Modulator 565740
Bryostatin 2 203812
Lipoxin A4 437720
L-α-Phosphatidylinositol-3,4,5-trisphosphate, Dipalmitoyl-, Heptaammonium Salt 524615
L-α-Phosphatidylinositol-3,4-bisphosphate, Dipalmitoyl-, Pentaammonium Salt 524613
L-α-Phosphatidylinositol-4,5-bisphosphate, Dipalmitoyl-, Pentaammonium Salt 524614
Oleic Acid - CAS 112-80-1 - Calbiochem 4954
Phorbol-12,13-dibutyrate 524390
Phorbol-12-myristate-13-acetate 524400

Assay Kits

Producto Formato Formulario Sensibilidad Rango de ensayo Tiempo de ensayo Tipo de muestra Núm. prod.
Protein Kinase Assay Kit, Non-Radioactive 96-well plate 96 Tests       Cell lysates, purified enzymes 539484

Enzymes

Producto Núm. prod.
PKC, Catalytic Subunit, Rat Brain 539513
PKCε, GST-Fusion, Human, Recombinant, S. frugiperda 539691
PKCα, His•Tag®, Human, Recombinant, S. frugiperda 539651
PKCθ, His•Tag®, Human, Recombinant, S. frugiperda 539677
PKCδ, Human, Recombinant, S. frugiperda 539672
PKCγ, Human, Recombinant, S. frugiperda 539665
PKCβI, Human, Recombinant, S. frugiperda 539655
PKCβII, His·Tag®, Human, Recombinant, S. frugiperda 539658
PKCβII, Human, Recombinant, S. frugiperda 539657
PKC, Rat Brain 539494
Protein Kinase Cζ, His·Tag®, Human, Recombinant, S. frugiperda 539679
Protein Kinase Cα, Human, Recombinant, S. frugiperda 539650
Protein Kinase C Isozyme Sampler Set 539674

Inhibitors

Producto Núm. prod.
Bisindolylmaleimide I - CAS 133052-90-1 - Calbiochem 203290
Bisindolylmaleimide I, Hydrochloride - CAS 176504-36-2 - Calbiochem 203291
Bisindolylmaleimide II - CAS 137592-45-1 - Calbiochem 203292
Bisindolylmaleimide III, Hydrochloride 203294
Bisindolylmaleimide IV - CAS 119139-23-0 - Calbiochem 203297
Bisindolylmaleimide V - CAS 113963-68-1 - Calbiochem 203303
Calphostin C, Cladosporium cladosporioides - CAS 121263-19-2 - Calbiochem 208725
Cardiotoxin, Naja nigricollis 217504
Chelerythrine Chloride - CAS 3895-92-9 - Calbiochem 220285
Dequalinium Chloride 263225
D-erythro-Sphingosine, Dihydro- 300230
D-erythro-Sphingosine, Free Base, High Purity 567726
D-erythro-Sphingosine, N,N-Dimethyl- - CAS 119567-63-4 - Calbiochem 310500
Ellagic Acid, Dihydrate - CAS 476-66-4 - Calbiochem 324683
Gö 6976 - CAS 136194-77-9 - Calbiochem 365250
Gö 6983 - CAS 133053-19-7 - Calbiochem 365251
Gö 7874, Hydrochloride - CAS 287935-76-6 - Calbiochem 365252
H-7, Dihydrochloride - CAS 108930-17-2 - Calbiochem 371955
HBDDE - CAS 154675-18-0 - Calbiochem 372770
Hispidin - CAS 555-55-5 - Calbiochem 377980
Hypericin - CAS 548-04-9 - Calbiochem 400076
InSolution™ Bisindolylmaleimide I - CAS 133052-90-1 - Calbiochem 203293
InSolution™ Gö 6976 - CAS 136194-77-9 - Calbiochem 365253
InSolution™ K-252a, Nocardiopsis sp. - CAS 97161-97-2 - Calbiochem 420297
InSolution™ Ro-31-8220 557521
Iso-H-7, Dihydrochloride 371956
K-252a, Nocardiopsis sp. - CAS 97161-97-2 - Calbiochem 420298
K-252b, Nocardiopsis sp. 420319
K-252c - CAS 85753-43-1 - Calbiochem 420305
Melittin 444605
NGIC-I 481500
Phloretin 524488
Piceatannol 527948
PKC 20-28, Cell-Permeable, Myristoylated 476480
PKCβII/EGFR Inhibitor 539652
PKCβ Inhibitor 539654
PKC Inhibitor, EGF-R Fragment 651-658, Myristoylated 476475
PKC Inhibitor Peptide 19-31 05-23-4904
PKC Inhibitor Peptide 19-36 539560
PKCθ Pseudosubstrate Inhibitor 539634
PKCζ/ι Pseudosubstrate Inhibitor 539610
PKCθ Pseudosubstrate Inhibitor, Myristoylated 539636
PKCη Pseudosubstrate Inhibitor, Myristoylated 539604
PKCζ Pseudosubstrate Inhibitor, Myristoylated 539624
PKCε Translocation Inhibitor Peptide 539522
PKCε Translocation Inhibitor Peptide, Negative Control 539542
Polymyxin B Sulfate - CAS 1405-20-5 - Calbiochem 5291
Ro-31-7549, Monohydrate 557508
Ro-31-8220 557520
Ro-31-8425 557514
Ro-32-0432 557525
Rottlerin 557370
Safingol 559300
Sangivamycin 559307
Staurosporine, N-Benzoyl 539648
Staurosporine, Streptomyces sp. 569397
Tamoxifen, 4-Hydroxy-, (Z)- 579002
Tamoxifen Citrate 579000
TER14687 581800
UCN-01 539644
UCN-02 539645
Vitamin E Succinate 679130

Peptides, Probes, and Substrates

Producto Núm. prod.
4EBP1/PHAS-I, Rat, Recombinant 516675
Histone H1, Calf Thymus 382150
MARCKS PSD-Derived Peptide, PKC Substrate 454880
PKCμ Peptide Substrate 539564
PKCε Peptide Substrate 539562
PKCδ Peptide Substrate 539563
PKCη Substrate, Biotinylated 539666
PKCζ Substrate, Biotinylated 539667
PKC Substrate, MBP 4-14 539492
Protein Kinase Cθ Substrate, Biotinylated 539668
RIM-1 557325
Syntide 2 05-23-4910

Recombinant Standards

Producto Núm. prod.
PKCβI Standard, Human, Recombinant, S. frugiperda 539619

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