PRKCD

Protein kinase C delta type (or PKC-δ) is an enzyme that in humans is encoded by the PRKCD gene.[5]

See also: Protein kinase C

PRKCD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YUU, 1YRK
Identifiers
Aliases	PRKCD, ALPS3, CVID9, MAY1, PKCD, nPKC-delta, protein kinase C delta
External IDs	OMIM: 176977 MGI: 97598 HomoloGene: 55963 GeneCards: PRKCD
EC number	2.7.10.2
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.1 Start 53,156,009 bp[1] End 53,192,717 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 B|14 18.82 cM Start 30,595,354 bp[2] End 30,626,210 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • kinase activity • ATP binding • protein kinase activity • non-membrane spanning protein tyrosine kinase activity • metal ion binding • kinase binding • enzyme binding • insulin receptor substrate binding • transferase activity • GO:0001948 protein binding • calcium-independent protein kinase C activity • protein kinase binding • nucleotide binding • GO:0010577 enzyme activator activity • protein serine/threonine kinase activity • protein kinase C activity Cellular component • cytoplasm • cytosol • membrane • intercellular junction • perinuclear region of cytoplasm • cell nucleus • nuclear matrix • endoplasmic reticulum • extracellular exosome • cell membrane • nucleoplasm • extracellular region • azurophil granule lumen Biological process • intrinsic apoptotic signaling pathway in response to oxidative stress • termination of signal transduction • interferon-gamma-mediated signaling pathway • negative regulation of protein binding • positive regulation of endodeoxyribonuclease activity • platelet activation • protein phosphorylation • cellular senescence • negative regulation of insulin receptor signaling pathway • positive regulation of sphingomyelin catabolic process • cell chemotaxis • cell cycle • negative regulation of inflammatory response • positive regulation of protein dephosphorylation • Fc-gamma receptor signaling pathway involved in phagocytosis • positive regulation of apoptotic signaling pathway • stimulatory C-type lectin receptor signaling pathway • cellular response to hydroperoxide • negative regulation of peptidyl-tyrosine phosphorylation • defense response to bacterium • negative regulation of MAP kinase activity • positive regulation of response to DNA damage stimulus • positive regulation of protein import into nucleus • interleukin-10 production • regulation of actin cytoskeleton organization • negative regulation of actin filament polymerization • regulation of mRNA stability • phosphorylation • protein stabilization • regulation of receptor activity • negative regulation of filopodium assembly • cellular response to angiotensin • interleukin-12 production • peptidyl-threonine phosphorylation • positive regulation of ceramide biosynthetic process • neutrophil activation • GO:0007243 intracellular signal transduction • negative regulation of glial cell apoptotic process • negative regulation of platelet aggregation • positive regulation of phospholipid scramblase activity • histone phosphorylation • B cell proliferation • immunoglobulin mediated immune response • positive regulation of glucosylceramide catabolic process • peptidyl-tyrosine phosphorylation • positive regulation of superoxide anion generation • activation of protein kinase activity • signal transduction • cellular response to hydrogen peroxide • peptidyl-serine phosphorylation • apoptotic process • neutrophil degranulation • execution phase of apoptosis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5580	18753
Ensembl	ENSG00000163932	ENSMUSG00000021948
UniProt	Q05655	P28867
RefSeq (mRNA)	NM_006254 NM_212539 NM_001316327 NM_001354676 NM_001354678 NM_001354679 NM_001354680	NM_011103 NM_001310682
RefSeq (protein)	NP_001303256 NP_006245 NP_997704 NP_001341605 NP_001341607 NP_001341608 NP_001341609	NP_001297611 NP_035233
Location (UCSC)	Chr 3: 53.16 – 53.19 Mb	Chr 14: 30.6 – 30.63 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messenger diacylglycerol.[6] PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. Studies both in human and mice demonstrate that this kinase is involved in B cell signaling and in the regulation of growth, apoptosis, and differentiation of a variety of cell types.[7] Protein kinase C delta is also regulated by phosphorylation on various serine/threonine (e.g. T50, T141, S304, T451, T505, S506, T507, S643, S664) and tyrosine residues including Y311 (by SRC).[8][9]

Interactions

PRKCD has been shown to interact with:

• C1QBP,[10]
• HER2/neu,[11]
• INSR,[12][13]
• MUC1,[14]
• mTOR,[15]
• PLD2,[16]
• PTPN6,[17]
• PTPRM,[18]
• PDPK1,[19]
• RASGRP3,[20]
• SHC1[21] and
• STAT1.[22]

References

1. GRCh38: Ensembl release 89: ENSG00000163932 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021948 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Huppi K, Siwarski D, Goodnight J, Mischak H (June 1994). "Assignment of the protein kinase C delta polypeptide gene (PRKCD) to human chromosome 3 and mouse chromosome 14". Genomics. 19 (1): 161–2. doi:10.1006/geno.1994.1028. PMID 8188219.
6. Kikkawa, Ushio (2002). "Protein Kinase Cδ (PKCδ): Activaton Mechanisms and Functions". The Journal of Biochemistry. 132 (6): 831–839. doi:10.1093/oxfordjournals.jbchem.a003294. Retrieved June 30, 2008.
7. "Entrez Gene: PRKCD protein kinase C, delta".
8. Welman A, Griffiths JR, Whetton AD, Dive C (December 2007). "Protein kinase C delta is phosphorylated on five novel Ser/Thr sites following inducible overexpression in human colorectal cancer cells". Protein Sci. 16 (12): 2711–5. doi:10.1110/ps.072874607. PMC 2222818. PMID 17965192.
9. Blake RA, Garcia-Paramio P, Parker PJ, Courtneidge SA (April 1999). "Src promotes PKCdelta degradation". Cell Growth Differ. 10 (4): 231–41. PMID 10319993.
10. Storz P, Hausser A, Link G, Dedio J, Ghebrehiwet B, Pfizenmaier K, Johannes FJ (August 2000). "Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32". J. Biol. Chem. 275 (32): 24601–7. doi:10.1074/jbc.M002964200. PMID 10831594.
11. Keshamouni, V. G. (17 April 2002). "Mechanism of 17-beta -Estradiol-induced Erk1/2 Activation in Breast Cancer Cells. A ROLE FOR HER2 AND PKC-delta". Journal of Biological Chemistry. 277 (25): 22558–22565. doi:10.1074/jbc.M202351200. PMID 11960991.
12. Braiman L, Alt A, Kuroki T, Ohba M, Bak A, Tennenbaum T, Sampson SR (April 2001). "Insulin induces specific interaction between insulin receptor and protein kinase C delta in primary cultured skeletal muscle". Mol. Endocrinol. 15 (4): 565–74. doi:10.1210/mend.15.4.0612. PMID 11266508.
13. Rosenzweig T, Braiman L, Bak A, Alt A, Kuroki T, Sampson SR (June 2002). "Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling". Diabetes. 51 (6): 1921–30. doi:10.2337/diabetes.51.6.1921. PMID 12031982.
14. Ren J, Li Y, Kufe D (May 2002). "Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling". J. Biol. Chem. 277 (20): 17616–22. doi:10.1074/jbc.M200436200. PMID 11877440.
15. Kumar V, Pandey P, Sabatini D, Kumar M, Majumder PK, Bharti A, Carmichael G, Kufe D, Kharbanda S (March 2000). "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation". EMBO J. 19 (5): 1087–97. doi:10.1093/emboj/19.5.1087. PMC 305647. PMID 10698949.
16. Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH (March 2002). "Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells". J. Biol. Chem. 277 (10): 8290–7. doi:10.1074/jbc.M108343200. PMID 11744693.
17. Yoshida K, Kufe D (December 2001). "Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase C delta in response to DNA damage". Mol. Pharmacol. 60 (6): 1431–8. doi:10.1124/mol.60.6.1431. PMID 11723252.
18. Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM (2011). "Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration". J. Cell. Biochem. 112 (1): 39–48. doi:10.1002/jcb.22710. PMC 3031780. PMID 20506511.
19. Hodgkinson CP, Sale GJ (January 2002). "Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C-terminal PRK2 fragment". Biochemistry. 41 (2): 561–9. doi:10.1021/bi010719z. PMID 11781095.
20. Brodie C, Steinhart R, Kazimirsky G, Rubinfeld H, Hyman T, Ayres JN, Hur GM, Toth A, Yang D, Garfield SH, Stone JC, Blumberg PM (July 2004). "PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters". Mol. Pharmacol. 66 (1): 76–84. doi:10.1124/mol.66.1.76. PMID 15213298.
21. Leitges M, Gimborn K, Elis W, Kalesnikoff J, Hughes MR, Krystal G, Huber M (June 2002). "Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Mol. Cell. Biol. 22 (12): 3970–80. doi:10.1128/mcb.22.12.3970-3980.2002. PMC 133855. PMID 12024011.
22. Kristof AS, Marks-Konczalik J, Billings E, Moss J (September 2003). "Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-gamma is regulated by mammalian target of rapamycin". J. Biol. Chem. 278 (36): 33637–44. doi:10.1074/jbc.M301053200. PMID 12807916.

Further reading

• Ali A, Hoeflich KP, Woodgett JR (2002). "Glycogen synthase kinase-3: properties, functions, and regulation". Chem. Rev. 101 (8): 2527–40. doi:10.1021/cr000110o. PMID 11749387.
• Slater SJ, Ho C, Stubbs CD (2003). "The use of fluorescent phorbol esters in studies of protein kinase C-membrane interactions". Chem. Phys. Lipids. 116 (1–2): 75–91. doi:10.1016/S0009-3084(02)00021-X. PMID 12093536.
• Brodie C, Blumberg PM (2003). "Regulation of cell apoptosis by protein kinase c delta". Apoptosis. 8 (1): 19–27. doi:10.1023/A:1021640817208. PMID 12510148.