PRKCI

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
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	Wikidata
View/Edit Human

Protein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.^[1]^[2]^[3]

Function

This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X.^[3]

Interactions

PRKCI has been shown to interact with:

Centaurin, alpha 1,^[4]
FRS2,^[5]
Glyceraldehyde 3-phosphate dehydrogenase,^[6]
PARD3,^[7]^[8]
Phosphoinositide-dependent kinase-1,^[9]
SMG1 (gene),^[10]
Sequestosome 1,
KRAS.^[11]

Vimentin ^[12]

^[13]

References

↑ Mazzarella R, Ciccodicola A, Esposito T, Arcucci A, Migliaccio C, Jones C, Schlessinger D, D'Urso M, D'Esposito M (Apr 1995). "Human protein kinase C Iota gene (PRKCI) is closely linked to the BTK gene in Xq21.3". Genomics. 26 (3): 629–31. doi:10.1016/0888-7543(95)80190-W. PMID 7607695.
↑ De Donato M, Gallagher DS, Davis SK, Stelly DM, Taylor JF (April 2002). "The assignment of PRKCI to bovine chromosome 1q34-->q36 by FISH suggests a new assignment to human chromosome 3". Cytogenetics and Cell Genetics. 95 (1–2): 79–81. doi:10.1159/000057021. PMID 11978974.
↑ ^3.0 ^3.1 "Entrez Gene: PRKCI protein kinase C, iota".
↑ Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (Aug 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochemical and Biophysical Research Communications. 307 (3): 459–65. doi:10.1016/s0006-291x(03)01187-2. PMID 12893243.
↑ Lim YP, Low BC, Lim J, Wong ES, Guy GR (Jul 1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". The Journal of Biological Chemistry. 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. PMID 10383403.
↑ Tisdale EJ (Feb 2002). "Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway". The Journal of Biological Chemistry. 277 (5): 3334–41. doi:10.1074/jbc.M109744200. PMID 11724794.
↑ Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–80. doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.
↑ Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H (Dec 2002). "PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions". Biochemical and Biophysical Research Communications. 299 (4): 641–6. doi:10.1016/s0006-291x(02)02698-0. PMID 12459187.
↑ Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (Jul 2000). "A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1". The Journal of Biological Chemistry. 275 (27): 20806–13. doi:10.1074/jbc.M000421200. PMID 10764742.
↑ Diaz-Meco MT, Municio MM, Sanchez P, Lozano J, Moscat J (Jan 1996). "Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo". Molecular and Cellular Biology. 16 (1): 105–14. PMC 230983. PMID 8524286.
↑ Guo W, Wu S, Liu J, Fang B (Sep 2008). "Identification of a small molecule with synthetic lethality for K-ras and protein kinase C iota". Cancer Research. 68 (18): 7403–8. doi:10.1158/0008-5472.CAN-08-1449. PMC 2678915. PMID 18794128.
↑ Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M (2017). "Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis". Int. J. Oncol. 51 (5): 1370–1382. doi:10.3892/ijo.2017.4131. PMC 5642393. PMID 29048609.
↑ Ratnayake WS, Apostolatos CA, Apostolatos AH, Schutte RJ, Huynh MA, Ostrov DA, Acevedo-Duncan M (2018). "Oncogenic PKC-ι activates Vimentin during epithelial-mesenchymal transition in melanoma; a study based on PKC-ι and PKC-ζ specific inhibitors". Cell Adhes. Migr. 0 (0): 1–17. doi:10.1080/19336918.2018.1471323. PMID 29781749.

Suzuki A, Akimoto K, Ohno S (Jan 2003). "Protein kinase C lambda/iota (PKClambda/iota): a PKC isotype essential for the development of multicellular organisms". Journal of Biochemistry. 133 (1): 9–16. doi:10.1093/jb/mvg018. PMID 12761193.
Fields AP, Regala RP (Jun 2007). "Protein kinase C iota: human oncogene, prognostic marker and therapeutic target". Pharmacological Research. 55 (6): 487–97. doi:10.1016/j.phrs.2007.04.015. PMC 2705893. PMID 17570678.
Ruegg CL, Strand M (Oct 1991). "A synthetic peptide with sequence identity to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and intracellular calcium influx". Cellular Immunology. 137 (1): 1–13. doi:10.1016/0008-8749(91)90051-C. PMID 1832084.
Chowdhury IH, Koyanagi Y, Kobayashi S, Hamamoto Y, Yoshiyama H, Yoshida T, Yamamoto N (May 1990). "The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway". Virology. 176 (1): 126–32. doi:10.1016/0042-6822(90)90237-L. PMID 1970444.
Ruegg CL, Strand M (May 1990). "Inhibition of protein kinase C and anti-CD3-induced Ca2+ influx in Jurkat T cells by a synthetic peptide with sequence identity to HIV-1 gp41". Journal of Immunology. 144 (10): 3928–35. PMID 2139676.
Jakobovits A, Rosenthal A, Capon DJ (Apr 1990). "Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C". The EMBO Journal. 9 (4): 1165–70. PMC 551792. PMID 2182321.
Fields AP, Bednarik DP, Hess A, May WS (May 1988). "Human immunodeficiency virus induces phosphorylation of its cell surface receptor". Nature. 333 (6170): 278–80. doi:10.1038/333278a0. PMID 3259291.
Chirmule N, Goonewardena H, Pahwa S, Pasieka R, Kalyanaraman VS, Pahwa S (Aug 1995). "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells". The Journal of Biological Chemistry. 270 (33): 19364–9. doi:10.1074/jbc.270.33.19364. PMID 7642615.
Ward NE, Gravitt KR, O'Brian CA (Jan 1995). "Inhibition of protein kinase C by a synthetic peptide corresponding to cytoplasmic domain residues 828-848 of the human immunodeficiency virus type 1 envelope glycoprotein". Cancer Letters. 88 (1): 37–40. doi:10.1016/0304-3835(94)03610-U. PMID 7850771.
Gupta S, Aggarwal S, Kim C, Gollapudi S (Mar 1994). "Human immunodeficiency virus-1 recombinant gp120 induces changes in protein kinase C isozymes--a preliminary report". International Journal of Immunopharmacology. 16 (3): 197–204. doi:10.1016/0192-0561(94)90013-2. PMID 8206685.
Selbie LA, Schmitz-Peiffer C, Sheng Y, Biden TJ (Nov 1993). "Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells". The Journal of Biological Chemistry. 268 (32): 24296–302. PMID 8226978.
Diaz-Meco MT, Municio MM, Sanchez P, Lozano J, Moscat J (Jan 1996). "Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo". Molecular and Cellular Biology. 16 (1): 105–14. PMC 230983. PMID 8524286.
Parada NA, Cruikshank WW, Danis HL, Ryan TC, Center DM (Feb 1996). "IL-16- and other CD4 ligand-induced migration is dependent upon protein kinase C". Cellular Immunology. 168 (1): 100–6. doi:10.1006/cimm.1996.0054. PMID 8599832.
Conant K, Ma M, Nath A, Major EO (Mar 1996). "Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kappa B binding and protein kinase C activity in primary human astrocytes". Journal of Virology. 70 (3): 1384–9. PMC 189957. PMID 8627654.
Díaz-Meco MT, Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L, Moscat J (Sep 1996). "The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C". Cell. 86 (5): 777–86. doi:10.1016/S0092-8674(00)80152-X. PMID 8797824.
Holmes AM (Nov 1996). "In vitro phosphorylation of human immunodeficiency virus type 1 Tat protein by protein kinase C: evidence for the phosphorylation of amino acid residue serine-46". Archives of Biochemistry and Biophysics. 335 (1): 8–12. doi:10.1006/abbi.1996.0476. PMID 8914829.
Murray NR, Fields AP (Oct 1997). "Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis". The Journal of Biological Chemistry. 272 (44): 27521–4. doi:10.1074/jbc.272.44.27521. PMID 9346882.
Borgatti P, Zauli G, Cantley LC, Capitani S (Jan 1998). "Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells". Biochemical and Biophysical Research Communications. 242 (2): 332–7. doi:10.1006/bbrc.1997.7877. PMID 9446795.
Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–80. doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.

[pmid7607695-1] Mazzarella R, Ciccodicola A, Esposito T, Arcucci A, Migliaccio C, Jones C, Schlessinger D, D'Urso M, D'Esposito M (Apr 1995). "Human protein kinase C Iota gene (PRKCI) is closely linked to the BTK gene in Xq21.3". Genomics. 26 (3): 629–31. doi:10.1016/0888-7543(95)80190-W. PMID 7607695.

[pmid11978974-2] De Donato M, Gallagher DS, Davis SK, Stelly DM, Taylor JF (April 2002). "The assignment of PRKCI to bovine chromosome 1q34-->q36 by FISH suggests a new assignment to human chromosome 3". Cytogenetics and Cell Genetics. 95 (1–2): 79–81. doi:10.1159/000057021. PMID 11978974.

[entrez-3] 3.0 ^3.1 "Entrez Gene: PRKCI protein kinase C, iota".

[pmid12893243-4] Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (Aug 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochemical and Biophysical Research Communications. 307 (3): 459–65. doi:10.1016/s0006-291x(03)01187-2. PMID 12893243.

[pmid10383403-5] Lim YP, Low BC, Lim J, Wong ES, Guy GR (Jul 1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". The Journal of Biological Chemistry. 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. PMID 10383403.

[pmid11724794-6] Tisdale EJ (Feb 2002). "Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway". The Journal of Biological Chemistry. 277 (5): 3334–41. doi:10.1074/jbc.M109744200. PMID 11724794.

[pmid9566925-7] Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–80. doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.

[pmid12459187-8] Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H (Dec 2002). "PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions". Biochemical and Biophysical Research Communications. 299 (4): 641–6. doi:10.1016/s0006-291x(02)02698-0. PMID 12459187.

[pmid10764742-9] Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (Jul 2000). "A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1". The Journal of Biological Chemistry. 275 (27): 20806–13. doi:10.1074/jbc.M000421200. PMID 10764742.

[pmid8524286-10] Diaz-Meco MT, Municio MM, Sanchez P, Lozano J, Moscat J (Jan 1996). "Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo". Molecular and Cellular Biology. 16 (1): 105–14. PMC 230983. PMID 8524286.

[pmid18794128-11] Guo W, Wu S, Liu J, Fang B (Sep 2008). "Identification of a small molecule with synthetic lethality for K-ras and protein kinase C iota". Cancer Research. 68 (18): 7403–8. doi:10.1158/0008-5472.CAN-08-1449. PMC 2678915. PMID 18794128.

[pmid29048609-12] Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M (2017). "Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis". Int. J. Oncol. 51 (5): 1370–1382. doi:10.3892/ijo.2017.4131. PMC 5642393. PMID 29048609.

[pmid29781749-13] Ratnayake WS, Apostolatos CA, Apostolatos AH, Schutte RJ, Huynh MA, Ostrov DA, Acevedo-Duncan M (2018). "Oncogenic PKC-ι activates Vimentin during epithelial-mesenchymal transition in melanoma; a study based on PKC-ι and PKC-ζ specific inhibitors". Cell Adhes. Migr. 0 (0): 1–17. doi:10.1080/19336918.2018.1471323. PMID 29781749.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

PRKCI

Contents

Function

Interactions

References

Further reading

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