4mjs

Structural highlights

Function

KPCZ_RAT Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukins production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In NF-kappa-B-mediated inflammatory response, can relieve the SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Is necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

See Also

• Protein kinase C 3D structures
• Sequestosome

References

1. ↑ Sacktor TC, Osten P, Valsamis H, Jiang X, Naik MU, Sublette E. Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8342-6. PMID:8378304
2. ↑ Berra E, Diaz-Meco MT, Lozano J, Frutos S, Municio MM, Sanchez P, Sanz L, Moscat J. Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta. EMBO J. 1995 Dec 15;14(24):6157-63. PMID:8557035
3. ↑ Standaert ML, Galloway L, Karnam P, Bandyopadhyay G, Moscat J, Farese RV. Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes. Potential role in glucose transport. J Biol Chem. 1997 Nov 28;272(48):30075-82. PMID:9374484
4. ↑ Puls A, Schmidt S, Grawe F, Stabel S. Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6191-6. PMID:9177193
5. ↑ Lallena MJ, Diaz-Meco MT, Bren G, Paya CV, Moscat J. Activation of IkappaB kinase beta by protein kinase C isoforms. Mol Cell Biol. 1999 Mar;19(3):2180-8. PMID:10022904
6. ↑ Sanz L, Diaz-Meco MT, Nakano H, Moscat J. The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway. EMBO J. 2000 Apr 3;19(7):1576-86. PMID:10747026 doi:10.1093/emboj/19.7.1576
7. ↑ Etienne-Manneville S, Hall A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell. 2001 Aug 24;106(4):489-98. PMID:11525734
8. ↑ Diaz-Meco MT, Moscat J. MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling. Mol Cell Biol. 2001 Feb;21(4):1218-27. PMID:11158308 doi:http://dx.doi.org/10.1128/MCB.21.4.1218-1227.2001
9. ↑ Ling DS, Benardo LS, Serrano PA, Blace N, Kelly MT, Crary JF, Sacktor TC. Protein kinase Mzeta is necessary and sufficient for LTP maintenance. Nat Neurosci. 2002 Apr;5(4):295-6. PMID:11914719 doi:http://dx.doi.org/10.1038/nn829
10. ↑ Ren J, Wang J, Wang Z, Wu J. Structural and biochemical insights into the homotypic PB1-PB1 complex between PKCzeta and p62. Sci China Life Sci. 2014 Jan;57(1):69-80. doi: 10.1007/s11427-013-4592-z. Epub, 2013 Dec 26. PMID:24369353 doi:http://dx.doi.org/10.1007/s11427-013-4592-z