4dc2

Structural highlights

Function

[KPCI_MOUSE] Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI3K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis (By similarity). Downstream of PI3K is required for insulin-stimulated glucose transport. Activates RAB4A and promotes its association with KIF3A which is required for the insulin-induced SLC2A4/GLUT4 translocation in adipocytes. Is essential in early embryogenesis and development of differentiating photoreceptors by playing a role in the establishment of epithelial and neuronal polarity.^{[1] [2] [3] [4] [5]}

See Also

• Protein kinase C 3D structures

References

1. ↑ Imamura T, Huang J, Usui I, Satoh H, Bever J, Olefsky JM. Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin. Mol Cell Biol. 2003 Jul;23(14):4892-900. PMID:12832475
2. ↑ Bandyopadhyay G, Standaert ML, Sajan MP, Kanoh Y, Miura A, Braun U, Kruse F, Leitges M, Farese RV. Protein kinase C-lambda knockout in embryonic stem cells and adipocytes impairs insulin-stimulated glucose transport. Mol Endocrinol. 2004 Feb;18(2):373-83. Epub 2003 Nov 13. PMID:14615604 doi:http://dx.doi.org/10.1210/me.2003-0087
3. ↑ Soloff RS, Katayama C, Lin MY, Feramisco JR, Hedrick SM. Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms. J Immunol. 2004 Sep 1;173(5):3250-60. PMID:15322187
4. ↑ Koike C, Nishida A, Akimoto K, Nakaya MA, Noda T, Ohno S, Furukawa T. Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina. J Neurosci. 2005 Nov 2;25(44):10290-8. PMID:16267237 doi:http://dx.doi.org/10.1523/JNEUROSCI.3657-05.2005
5. ↑ Uberall F, Hellbert K, Kampfer S, Maly K, Villunger A, Spitaler M, Mwanjewe J, Baier-Bitterlich G, Baier G, Grunicke HH. Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton. J Cell Biol. 1999 Feb 8;144(3):413-25. PMID:9971737
6. ↑ Wang C, Shang Y, Yu J, Zhang M. Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3. Structure. 2012 May 9;20(5):791-801. PMID:22579248 doi:10.1016/j.str.2012.02.022