protein kinase C alpha | Delta subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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protein kinase C alpha

target has curated data in GtoImmuPdb

Target id: 1482

Nomenclature: protein kinase C alpha

Abbreviated Name: PKCα

Family: Delta subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 672 17q22-q24 PRKCA protein kinase C alpha
Mouse - 672 11 E1 Prkca protein kinase C, alpha
Rat - 672 10q32.1 Prkca protein kinase C, alpha
Previous and Unofficial Names
PKC-alpha | protein kinase C
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.13

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ingenol mebutate Hs Activation 9.5 pKi 8
pKi 9.5 (Ki 3x10-10 M) [8]
RasGRP activator 1 Hs Binding 7.8 pKi 6
pKi 7.8 (Ki 1.62x10-8 M) [6]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sotrastaurin Hs Inhibition 8.7 pIC50 13
pIC50 8.7 (IC50 2.1x10-9 M) [13]
Gö 6976 Hs Inhibition 8.6 pIC50 9
pIC50 8.6 (IC50 2.3x10-9 M) [9]
Gö 6983 Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 7x10-9 M) [7]
Ro-32-0432 Bt Inhibition 8.0 – 8.1 pIC50 2,14
pIC50 8.0 – 8.1 (IC50 9.3x10-9 – 9x10-9 M) [2,14]
GF109203X Bt Inhibition 7.7 pIC50 12
pIC50 7.7 (IC50 2x10-8 M) [12]
7-hydroxystaurosporine Hs Inhibition 7.5 pIC50 10
pIC50 7.5 (IC50 2.9x10-8 M) [10]
balanol Hs Inhibition 7.5 pIC50 3
pIC50 7.5 (IC50 3x10-8 M) [3]
ruboxistaurin Hs Inhibition 6.4 pIC50 11
pIC50 6.4 (IC50 3.6x10-7 M) [11]
enzastaurin Hs Inhibition 6.1 pIC50 4
pIC50 6.1 (IC50 8x10-7 M) [4]
View species-specific inhibitor tables
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: PKCα/PKCa
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.2 0.5 -0.5
Ro-32-0432 Hs Inhibitor Inhibition 2.6
Gö 6983 Hs Inhibitor Inhibition 3.1 -1.0 0.0
GF109203X Hs Inhibitor Inhibition 6.3 1.0 1.0
Gö 6976 Hs Inhibitor Inhibition 7.6 1.0 3.0
SB 218078 Hs Inhibitor Inhibition 13.9 96.0 98.0
K-252a Hs Inhibitor Inhibition 23.7 19.0 0.0
bisindolylmaleimide IV Hs Inhibitor Inhibition 27.7 26.0 4.0
midostaurin Hs Inhibitor Inhibition 27.7 36.0 14.0
PKCbeta inhibitor Hs Inhibitor Inhibition 32.0 6.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCα is included in GtoImmuPdb based on its GO immune process associations.
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0045651 positive regulation of macrophage differentiation ISS
GO:0050729 positive regulation of inflammatory response IMP
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045651 positive regulation of macrophage differentiation ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0070555 response to interleukin-1 IMP
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0048259 regulation of receptor-mediated endocytosis ISO
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0030593 neutrophil chemotaxis IMP
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0030593 neutrophil chemotaxis IMP
GO:0050729 positive regulation of inflammatory response IMP

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Birchall AM, Bishop J, Bradshaw D, Cline A, Coffey J, Elliott LH, Gibson VM, Greenham A, Hallam TJ, Harris W et al.. (1994) Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. J. Pharmacol. Exp. Ther., 268 (2): 922-9. [PMID:8114006]

3. Defauw JM, Murphy MM, Jagdmann Jr GE, Hu H, Lampe JW, Hollinshead SP, Mitchell TJ, Crane HM, Heerding JM, Mendoza JS et al.. (1996) Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J. Med. Chem., 39 (26): 5215-27. [PMID:8978850]

4. Faul MM, Gillig JR, Jirousek MR, Ballas LM, Schotten T, Kahl A, Mohr M. (2003) Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCbeta. Bioorg. Med. Chem. Lett., 13 (11): 1857-9. [PMID:12749884]

5. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

6. Garcia LC, Donadío LG, Mann E, Kolusheva S, Kedei N, Lewin NE, Hill CS, Kelsey JS, Yang J, Esch TE et al.. (2014) Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorg. Med. Chem., 22 (12): 3123-40. [PMID:24794745]

7. Gschwendt M, Dieterich S, Rennecke J, Kittstein W, Mueller HJ, Johannes FJ. (1996) Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett., 392 (2): 77-80. [PMID:8772178]

8. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM. (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res., 64 (9): 3243-55. [PMID:15126366]

9. Martiny-Baron G, Kazanietz MG, Mischak H, Blumberg PM, Kochs G, Hug H, Marmé D, Schächtele C. (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976. J. Biol. Chem., 268 (13): 9194-7. [PMID:8486620]

10. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA, Worland PJ. (1994) Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol. Pharmacol., 45 (6): 1207-14. [PMID:8022414]

11. Tanaka M, Sagawa S, Hoshi J, Shimoma F, Matsuda I, Sakoda K, Sasase T, Shindo M, Inaba T. (2004) Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. Bioorg. Med. Chem. Lett., 14 (20): 5171-4. [PMID:15380221]

12. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F et al.. (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J. Biol. Chem., 266 (24): 15771-81. [PMID:1874734]

13. Wagner J, von Matt P, Sedrani R, Albert R, Cooke N, Ehrhardt C, Geiser M, Rummel G, Stark W, Strauss A et al.. (2009) Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. J. Med. Chem., 52 (20): 6193-6. [PMID:19827831]

14. Wilkinson SE, Parker PJ, Nixon JS. (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem. J., 294 ( Pt 2): 335-7. [PMID:8373348]

How to cite this page

Delta subfamily: protein kinase C alpha. Last modified on 28/08/2018. Accessed on 12/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1482.