Protein kinase C zeta type
Also known as: PKC2, PRKCZ
Function
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 the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin 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 the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.
Classification
- Family (Pfam)
- PF00130 C1_1, PF00564 PB1, PF00069 Pkinase, PF00433 Pkinase_C
- InterPro
- AGC-kinase_C, aPKC_zeta, C1-like_sf, C1_aPKC_zeta, DAG/PE-bd, Kinase-like_dom_sf, PB1-like, PB1_aPKC, PB1_dom, PKC, PKC_DAG/PE, Pkinase_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Serine/Threonine Protein Kinases
Gene Ontology · 47
- GO:0045179 apical cortex
- GO:0016324 apical plasma membrane
- GO:0043203 axon hillock
- GO:0005923 bicellular tight junction
- GO:0030054 cell junction
- GO:0005911 cell-cell junction
- GO:0005929 cilium
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005768 endosome
- GO:0070062 extracellular exosome
- GO:0016020 membrane
- GO:0005815 microtubule organizing center
- GO:0035748 myelin sheath abaxonal region
- GO:0005635 nuclear envelope
- GO:0016363 nuclear matrix
- GO:0005886 plasma membrane
- GO:0070160 tight junction
- GO:0031982 vesicle
- GO:0005524 ATP binding
- GO:0004698 calcium,diacylglycerol-dependent serine/threonine kinase activity
- GO:0004697 diacylglycerol-dependent serine/threonine kinase activity
- GO:0043560 insulin receptor substrate binding
- GO:0004672 protein kinase activity
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0008270 zinc ion binding
- GO:0032869 cellular response to insulin stimulus
- GO:0030010 establishment of cell polarity
- GO:0006954 inflammatory response
- GO:0035556 intracellular signal transduction
- GO:0060291 long-term synaptic potentiation
- GO:0043066 negative regulation of apoptotic process
- GO:0046627 negative regulation of insulin receptor signaling pathway
- GO:0031333 negative regulation of protein-containing complex assembly
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:2000463 positive regulation of excitatory postsynaptic potential
- GO:0046628 positive regulation of insulin receptor signaling pathway
- GO:0032733 positive regulation of interleukin-10 production
- GO:0032736 positive regulation of interleukin-13 production
- GO:0032753 positive regulation of interleukin-4 production
- GO:0032754 positive regulation of interleukin-5 production
- GO:2000553 positive regulation of T-helper 2 cell cytokine production
- GO:0045630 positive regulation of T-helper 2 cell differentiation
- GO:0072659 protein localization to plasma membrane
- GO:0006468 protein phosphorylation
- GO:0007165 signal transduction
Drugs targeting this protein · 5
- GSK-690693 inhibitor
- SOTRASTAURIN inhibitor
- UCN-01 inhibitor
- CEP-2563 DIHYDROCHLORIDE inhibitor
- MIDOSTAURIN inhibitor
Related proteins · sequence + function similarity
- Protein kinase C zeta type 0.99
- Protein kinase C zeta type 0.99
- Protein kinase C zeta type 0.99
- Protein kinase C iota type 0.97
- Protein kinase C iota type 0.96
- Protein kinase C iota type 0.96
- Protein kinase C iota type 0.96
- Protein kinase C iota type 0.96
- Protein kinase C-like 3 0.94
- Protein kinase C-like 3 0.92
- Atypical protein kinase C 0.92
- Protein kinase C theta type 0.82
Co-cited proteins · studied together in the literature
- Serine/threonine-protein kinase STK11 2 shared papers
- Protein kinase C gamma type 2 shared papers
- Serine/threonine-protein kinase MARK2 2 shared papers
- Protein kinase C iota type 6 shared papers
- RAC-gamma serine/threonine-protein kinase 1 shared papers
- Partitioning defective 6 homolog beta 2 shared papers
- Protein KIBRA 1 shared papers
- PRKC apoptosis WT1 regulator protein 1 shared papers
- 3-phosphoinositide-dependent protein kinase 1 1 shared papers
- 3-phosphoinositide-dependent protein kinase 1 1 shared papers
- Protein KIBRA 2 shared papers
- Protein WWC2 1 shared papers
Literature · 39 cited papers
- PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain. Biochem. J. · 2022
- Withdrawal: Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J. Biol. Chem. · 2019
- APPL proteins promote TGFbeta-induced nuclear transport of the TGFbeta type I receptor intracellular domain. Oncotarget · 2016
- Evolutionary and Molecular Facts Link the WWC Protein Family to Hippo Signaling. Mol. Biol. Evol. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J. Cell Sci. · 2010
- Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
- A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
- Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J. Biol. Chem. · 2008
- KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. Biochim. Biophys. Acta · 2008
- Patterns of somatic mutation in human cancer genomes. Nature · 2007
- … and 27 more in the literature graph