2fk9

Structural highlights

Disease

KPCL_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry.

Function

KPCL_HUMAN Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Protein kinase C 3D structures

References

1. ↑ Akkaraju GR, Basu A. Overexpression of protein kinase C-eta attenuates caspase activation and tumor necrosis factor-alpha-induced cell death. Biochem Biophys Res Commun. 2000 Dec 9;279(1):103-7. PMID:11112424 doi:http://dx.doi.org/10.1006/bbrc.2000.3903
2. ↑ Hussaini IM, Karns LR, Vinton G, Carpenter JE, Redpath GT, Sando JJ, VandenBerg SR. Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells. J Biol Chem. 2000 Jul 21;275(29):22348-54. PMID:10806212 doi:http://dx.doi.org/10.1074/jbc.M003203200
3. ↑ Hussaini IM, Carpenter JE, Redpath GT, Sando JJ, Shaffrey ME, Vandenberg SR. Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation. Neuro Oncol. 2002 Jan;4(1):9-21. PMID:11772428
4. ↑ Aeder SE, Martin PM, Soh JW, Hussaini IM. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene. 2004 Dec 2;23(56):9062-9. PMID:15489897 doi:http://dx.doi.org/10.1038/sj.onc.1208093
5. ↑ Uht RM, Amos S, Martin PM, Riggan AE, Hussaini IM. The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene. 2007 May 3;26(20):2885-93. Epub 2006 Dec 4. PMID:17146445 doi:http://dx.doi.org/10.1038/sj.onc.1210090
6. ↑ Oda A, Ono T, Yamamoto M, Goitsuka R, Kitamura D. PKC eta directs induction of IRF-4 expression and Ig kappa gene rearrangement in pre-BCR signaling pathway. Int Immunol. 2008 Nov;20(11):1417-26. doi: 10.1093/intimm/dxn101. Epub 2008 Sep, 9. PMID:18780722 doi:http://dx.doi.org/10.1093/intimm/dxn101
7. ↑ Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R, Rao R. PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):61-6. doi: 10.1073/pnas.0802741106., Epub 2008 Dec 29. PMID:19114660 doi:10.1073/pnas.0802741106
8. ↑ Lee HK, Yeo S, Kim JS, Lee JG, Bae YS, Lee C, Baek SH. Protein kinase C-eta and phospholipase D2 pathway regulates foam cell formation via regulator of G protein signaling 2. Mol Pharmacol. 2010 Sep;78(3):478-85. doi: 10.1124/mol.110.064394. Epub 2010 Jun , 17. PMID:20558593 doi:http://dx.doi.org/10.1124/mol.110.064394
9. ↑ Raveh-Amit H, Hai N, Rotem-Dai N, Shahaf G, Gopas J, Livneh E. Protein kinase Ceta activates NF-kappaB in response to camptothecin-induced DNA damage. Biochem Biophys Res Commun. 2011 Aug 26;412(2):313-7. doi:, 10.1016/j.bbrc.2011.07.090. Epub 2011 Jul 28. PMID:21820409 doi:http://dx.doi.org/10.1016/j.bbrc.2011.07.090
10. ↑ Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA. PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 2012 Feb 3;148(3):543-55. doi: 10.1016/j.cell.2012.01.016. PMID:22304920 doi:http://dx.doi.org/10.1016/j.cell.2012.01.016
11. ↑ Littler DR, Walker JR, She YM, Finerty PJ Jr, Newman EM, Dhe-Paganon S. Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites. Biochem Biophys Res Commun. 2006 Nov 3;349(4):1182-9. Epub 2006 Sep 5. PMID:16973127 doi:10.1016/j.bbrc.2006.08.160