PKCZ 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'. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro. Isoform 2: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Expressed in brain, and to a lesser extent in lung, kidney and testis. 3 human isoforms generated by alternative promoter usage or alternative splicing have been reported. Note: This description may include information from UniProtKB.
Protein type: AGC group; EC; Kinase, protein; PKC family; PKCi subfamily; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of rat Ortholog: 5q36
Cellular Component:  apical cortex; apical plasma membrane; axon hillock; bicellular tight junction; cell cortex; cell leading edge; cell-cell junction; cytoplasm; cytosol; endosome; glutamatergic synapse; microtubule organizing center; myelin sheath abaxonal region; nuclear envelope; nuclear matrix; nucleus; perinuclear region of cytoplasm; plasma membrane; postsynaptic density; Schaffer collateral - CA1 synapse; stress fiber; vesicle
Molecular Function:  14-3-3 protein binding; ATP binding; calcium-dependent protein kinase C activity; metal ion binding; phospholipase binding; potassium channel regulator activity; protein binding; protein kinase activity; protein kinase binding; protein kinase C activity; protein serine kinase activity; protein serine/threonine kinase activity; protein-containing complex binding
Biological Process:  activation of phospholipase D activity; activation of protein kinase B activity; cell migration; cell surface receptor signaling pathway; cellular response to insulin stimulus; establishment of cell polarity; inflammatory response; intracellular signal transduction; long-term memory; long-term synaptic potentiation; membrane depolarization; membrane hyperpolarization; microtubule cytoskeleton organization; negative regulation of apoptotic process; negative regulation of hydrolase activity; negative regulation of insulin receptor signaling pathway; negative regulation of peptidyl-tyrosine phosphorylation; negative regulation of protein-containing complex assembly; neuron projection extension; peptidyl-serine phosphorylation; positive regulation of cell population proliferation; positive regulation of cell-matrix adhesion; positive regulation of ERK1 and ERK2 cascade; positive regulation of excitatory postsynaptic potential; positive regulation of insulin receptor signaling pathway; positive regulation of interleukin-10 production; positive regulation of interleukin-13 production; positive regulation of interleukin-4 production; positive regulation of interleukin-5 production; positive regulation of NF-kappaB transcription factor activity; positive regulation of protein transport; positive regulation of synaptic transmission; positive regulation of T-helper 2 cell cytokine production; positive regulation of T-helper 2 cell differentiation; protein kinase C signaling; protein localization to plasma membrane; protein phosphorylation; regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; vesicle transport along microtubule
Reference #:  P09217 (UniProtKB)
Alt. Names/Synonyms: 14 - 3 - 3 - zeta isoform; 14-3-3-zetaisoform; KPCZ; nPKC-zeta; Pkcz; PKM zeta; PKMzeta; Prkcz; Protein kinase C zeta type; protein kinase C, zeta; protein kinase M, zeta; r14-3-3
Gene Symbols: Prkcz
Molecular weight: 67,733 Da
Basal Isoelectric point: 5.47  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  Mitochondrial Control of Apoptosis  |  NF-kB Signaling  |  Phospholipase Signaling  |  Protein Kinase C Signaling  |  TGF-ß Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene