PRKCD

Protein kinase C, delta
PDB rendering based on 1bdy.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1YRK​, 2YUU​
Identifiers
Symbols	PRKCD ; ALPS3; CVID9; MAY1; PKCD; nPKC-delta
External IDs	OMIM: 176977 MGI: 97598 HomoloGene: 55963 ChEMBL: 2996 GeneCards: PRKCD Gene
EC number	2.7.10.2, 2.7.11.13
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • protein kinase C activity • calcium-independent protein kinase C activity • non-membrane spanning protein tyrosine kinase activity • protein binding • ATP binding • enzyme activator activity • enzyme binding • insulin receptor substrate binding • metal ion binding Cellular component • nucleus • nucleoplasm • cytoplasm • mitochondrion • endoplasmic reticulum • cytosol • plasma membrane • cell-cell junction • nuclear matrix • perinuclear region of cytoplasm • extracellular exosome Biological process • stimulatory C-type lectin receptor signaling pathway • protein phosphorylation • apoptotic process • cellular component disassembly involved in execution phase of apoptosis • cell cycle • signal transduction • epidermal growth factor receptor signaling pathway • activation of phospholipase C activity • blood coagulation • fibroblast growth factor receptor signaling pathway • intrinsic apoptotic signaling pathway in response to oxidative stress • gene expression • regulation of receptor activity • programmed cell death • immunoglobulin mediated immune response • peptidyl-threonine phosphorylation • peptidyl-tyrosine phosphorylation • cytokine-mediated signaling pathway • termination of signal transduction • platelet activation • negative regulation of actin filament polymerization • negative regulation of protein binding • interleukin-10 production • interleukin-12 production • positive regulation of superoxide anion generation • regulation of actin cytoskeleton organization • negative regulation of glial cell apoptotic process • positive regulation of protein dephosphorylation • Fc-gamma receptor signaling pathway involved in phagocytosis • B cell proliferation • neutrophil activation • defense response to bacterium • negative regulation of MAP kinase activity • innate immune response • negative regulation of insulin receptor signaling pathway • vascular endothelial growth factor receptor signaling pathway • neurotrophin TRK receptor signaling pathway • negative regulation of inflammatory response • negative regulation of peptidyl-tyrosine phosphorylation • protein stabilization • negative regulation of filopodium assembly • cell chemotaxis • interferon-gamma-mediated signaling pathway • negative regulation of platelet aggregation • cellular senescence • positive regulation of phospholipid scramblase activity • positive regulation of ceramide biosynthetic process • positive regulation of glucosylceramide catabolic process • positive regulation of sphingomyelin catabolic process • positive regulation of response to DNA damage stimulus • positive regulation of apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5580	18753
Ensembl	ENSG00000163932	ENSMUSG00000021948
UniProt	Q05655	P28867
RefSeq (mRNA)	NM_006254	NM_011103
RefSeq (protein)	NP_006245	NP_035233
Location (UCSC)	Chr 3: 53.16 – 53.19 Mb	Chr 14: 30.6 – 30.63 Mb
PubMed search

Protein kinase C delta type is an enzyme that in humans is encoded by the PRKCD gene.^[1]

Function

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. 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.^[2] 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).^[3][4]

Interactions

PRKCD has been shown to interact with:

• C1QBP,^[5]
• INSR,^[6][7]
• MUC1,^[8]
• MTOR,^[9]
• PLD2,^[10]
• PTPN6,^[11]
• PTPRM,^[12]
• PDPK1,^[13]
• RASGRP3,^[14]
• SHC1^[15] and
• STAT1.^[16]

References

1. 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.
2. "Entrez Gene: PRKCD protein kinase C, delta".
3. 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.
4. Blake RA, Garcia-Paramio P, Parker PJ, Courtneidge SA (April 1999). "Src promotes PKCdelta degradation". Cell Growth Differ. 10 (4): 231–41. PMID 10319993.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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. PMID 11723252.
12. Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM. "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.
13. 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.
14. 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.
15. 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.
16. 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.