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protein kinase C beta

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Target id: 1483

Nomenclature: protein kinase C beta

Abbreviated Name: PKCβ

Family: Alpha subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 671 16p12.2-p12.1 PRKCB protein kinase C beta
Mouse - 671 7 65.75 cM Prkcb protein kinase C, beta
Rat - 671 1q36 Prkcb protein kinase C, beta
Gene and Protein Information Comments
The human PKCβ listed here is the longer isoform 2 (aka PKCβ2). A shorter isoform, PKCβ1, with 671 amino acids exists (isoform 1) and has RefSeq protein ID NP_997700.
Previous and Unofficial Names Click here for help
PRKCB1 | PRKCB2 | PKC-beta | protein kinase C beta I | protein kinase C beta II | protein kinase C
Database Links Click here for help
Alphafold P05771 (Hs), P68404 (Mm), P68403 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL3045 (Hs), CHEMBL3042 (Mm), CHEMBL3020 (Rn)
Ensembl Gene ENSG00000166501 (Hs), ENSMUSG00000052889 (Mm), ENSRNOG00000012061 (Rn)
Entrez Gene 5579 (Hs), 18751 (Mm), 25023 (Rn)
Human Protein Atlas ENSG00000166501 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5579 (Hs), mmu:18751 (Mm), rno:25023 (Rn)
OMIM 176970 (Hs)
Pharos P05771 (Hs)
RefSeq Nucleotide NM_002738 (Hs), NM_008855 (Mm), NM_001172305 (Rn)
RefSeq Protein NP_002729 (Hs), NP_032881 (Mm), NP_001165776 (Rn)
UniProtKB P05771 (Hs), P68404 (Mm), P68403 (Rn)
Wikipedia PRKCB (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.13

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ingenol mebutate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Activation 10.0 pKi 9
⤷ pKi 10.0 (Ki 1.05x10-10 M) [9]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sotrastaurin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 14
⤷ pIC50 8.7 (IC50 2x10-9 M) [14]
PKCbeta inhibitor Small molecule or natural product Primary target of this compound Hs Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5x10-9 M) [12]
ruboxistaurin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 8
⤷ pIC50 8.2 (IC50 5.9x10-9 M) [8]
Gö 6983 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 7x10-9 M) [7]
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 4
⤷ pIC50 8.0 (IC50 1x10-8 M) [4]
GF109203X Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Bt Inhibition 7.8 pIC50 13
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [13]
7-hydroxystaurosporine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 11
⤷ pIC50 7.5 (IC50 3.4x10-8 M) [11]
enzastaurin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 5
⤷ pIC50 7.5 (IC50 3x10-8 M) [5]
Ro-32-0432 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Bt Inhibition 7.5 – 7.5 pIC50 2,15
⤷ pIC50 7.5 – 7.5 (IC50 3.1x10-8 – 3x10-8 M) [2,15]
bisindolylmaleimide IV Small molecule or natural product Primary target of this compound Hs Inhibition 6.7 pIC50 12
⤷ pIC50 6.7 (IC50 2.12x10-7 M) [12]
Description: PKCβ2 isoform
CGP53353 Small molecule or natural product Hs Inhibition 6.4 pIC50 3
⤷ pIC50 6.4 (IC50 3.98x10-7 M) [3]
View species-specific inhibitor tables
Inhibitor Comments
Bisindolylmaleimide IV also inhibits the shorter isoform of PKCβ, PKCβ1 with an IC50 value of 304nM [12].
Gö 6976 inhibits human PKCβ1 with an IC50 value of 6.2nM [10].
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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: 1,6
Key to terms and symbols Click column headers to sort
Target used in screen: PKCβI/PKCb1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.2 4.0 1.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 3.7
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.1 1.0 1.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 9.8 19.0 2.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 18.7 6.0 6.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 19.3 4.0 -1.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 22.4 66.0 14.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 22.5 95.0 91.0
bisindolylmaleimide IV Small molecule or natural product Hs Inhibitor Inhibition 26.1 66.0 23.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 26.3 53.0 13.0
Target used in screen: PKCβII/PKCb2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 2.3
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.0 3.5 2.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 4.3 27.0 6.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 6.4 112.0 108.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.5 61.0 45.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 23.0 29.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.6 9.0 2.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 13.8 67.0 18.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 14.2 4.0 3.0
CGP53353 Small molecule or natural product Hs Inhibitor Inhibition 15.5 93.0 103.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
Immuno Process Associations
Immuno Process:  Immune system development
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)

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. Chalfant CE, Ohno S, Konno Y, Fisher AA, Bisnauth LD, Watson JE, Cooper DR. (1996) A carboxy-terminal deletion mutant of protein kinase C beta II inhibits insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells. Mol Endocrinol, 10 (10): 1273-81. [PMID:9121494]

4. 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]

5. 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]

6. 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]

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. Jirousek MR, Gillig JR, Gonzalez CM, Heath WF, McDonald JH, Neel DA, Rito CJ, Singh U, Stramm LE, Melikian-Badalian A et al.. (1996) (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem, 39 (14): 2664-71. [PMID:8709095]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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

Alpha subfamily: protein kinase C beta. Last modified on 22/03/2017. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1483.