Pyk2 Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. Most abundant in the brain, with highest levels in amygdala and hippocampus. Low levels in kidney (at protein level). Also expressed in spleen and lymphocytes. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.2; Fak family; Kinase, protein; Nuclear receptor co-regulator; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group
Chromosomal Location of Human Ortholog: 8p21.2
Cellular Component:  apical dendrite; cell body; cell cortex; cytoplasm; cytoskeleton; cytosol; dendrite; extrinsic component of cytoplasmic side of plasma membrane; focal adhesion; glutamatergic synapse; growth cone; lamellipodium; membrane raft; neuronal cell body; NMDA selective glutamate receptor complex; nucleus; perinuclear region of cytoplasm; postsynaptic density
Molecular Function:  3-phosphoinositide-dependent protein kinase binding; ATP binding; calmodulin-dependent protein kinase activity; non-membrane spanning protein tyrosine kinase activity; protein binding; protein C-terminus binding; protein tyrosine kinase activity; protein-containing complex binding; ubiquitin protein ligase binding
Biological Process:  activation of GTPase activity; activation of Janus kinase activity; adaptive immune response; apoptotic process; blood vessel endothelial cell migration; bone resorption; cell surface receptor signaling pathway; cellular defense response; cellular response to fluid shear stress; cellular response to retinoic acid; chemokine-mediated signaling pathway; focal adhesion assembly; glial cell proliferation; integrin-mediated signaling pathway; interleukin-2-mediated signaling pathway; ionotropic glutamate receptor signaling pathway; long-term synaptic depression; long-term synaptic potentiation; MAPK cascade; marginal zone B cell differentiation; negative regulation of apoptotic process; negative regulation of bone mineralization; negative regulation of cell proliferation; negative regulation of muscle cell apoptotic process; negative regulation of myeloid cell differentiation; negative regulation of neuron apoptotic process; negative regulation of potassium ion transport; neuron projection development; oocyte maturation; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; positive regulation of actin filament polymerization; positive regulation of angiogenesis; positive regulation of B cell chemotaxis; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cell-matrix adhesion; positive regulation of cytosolic calcium ion concentration; positive regulation of DNA biosynthetic process; positive regulation of endothelial cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of excitatory postsynaptic potential; positive regulation of JNK cascade; positive regulation of JUN kinase activity; positive regulation of neuron projection development; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase activity; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of protein kinase activity; positive regulation of synaptic transmission, glutamatergic; positive regulation of translation; positive regulation of ubiquitin-dependent protein catabolic process; protein autophosphorylation; protein phosphorylation; protein-containing complex assembly; regulation of actin cytoskeleton reorganization; regulation of calcium-mediated signaling; regulation of cell adhesion; regulation of cell shape; regulation of cGMP-mediated signaling; regulation of establishment of cell polarity; regulation of inositol trisphosphate biosynthetic process; regulation of macrophage chemotaxis; regulation of NMDA receptor activity; regulation of release of sequestered calcium ion into cytosol; regulation of synaptic plasticity; regulation of ubiquitin-dependent protein catabolic process; response to calcium ion; response to cAMP; response to cocaine; response to ethanol; response to glucose; response to hormone; response to hydrogen peroxide; response to hypoxia; response to immobilization stress; response to lithium ion; response to mechanical stimulus; response to osmotic stress; signal complex assembly; signal transduction; sprouting angiogenesis; stress fiber assembly; tumor necrosis factor-mediated signaling pathway; vascular endothelial growth factor receptor signaling pathway
Reference #:  Q14289 (UniProtKB)
Alt. Names/Synonyms: CADTK; CAK beta; CAK-beta; CAKB; Calcium-dependent tyrosine kinase; Cell adhesion kinase beta; FADK 2; FADK2; FAK2; Focal adhesion kinase 2; PKB; Proline-rich tyrosine kinase 2; protein kinase B; protein tyrosine kinase 2 beta; Protein-tyrosine kinase 2-beta; PTK; PTK2B; PTK2B protein tyrosine kinase 2 beta; PYK2; RAFTK; Related adhesion focal tyrosine kinase
Gene Symbols: PTK2B
Molecular weight: 115,875 Da
Basal Isoelectric point: 5.91  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Pyk2

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