Background: | 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 Ca2+ 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. |
Synonyms: | CADTK; CAK beta; Calcium-dependent tyrosine kinase; Cell adhesion kinase beta; EC 2.7.10.2 |
UniProt Protein Function: | Pyk2: a nonreceptor tyrosine kinase of the Fak family. Predominantly expressed in the cells derived from hematopoietic lineages and in the central nervous system. Pyk2 is one of the signaling mediators for G-protein-coupled receptors. Involved in calcium induced regulation of ion channel and activation of the map kinase signaling pathway. Interacts with the SH2 domain of Grb2. May phosphorylate the voltage-gated potassium channel protein Kv1.2. Its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity. It plays an important role in cell motility such as spreading and migration. Two alternatively spliced isoforms have been described. |
UniProt Protein Details: | Protein type:Nuclear receptor co-regulator; Protein kinase, TK; Kinase, protein; EC 2.7.10.2; Protein kinase, tyrosine (non-receptor); TK group; Fak family Chromosomal Location of Human Ortholog: 8p21.1 Cellular Component: axon; cell cortex; cell soma; cytoplasm; cytoskeleton; cytosol; dendrite; extrinsic to internal side of plasma membrane; focal adhesion; growth cone; lamellipodium; lipid raft; N-methyl-D-aspartate selective glutamate receptor complex; nucleoplasm; nucleus; perinuclear region of cytoplasm; postsynaptic density Molecular Function:3-phosphoinositide-dependent protein kinase binding; ATP binding; calmodulin-dependent protein kinase activity; N-methyl-D-aspartate selective glutamate receptor activity; non-membrane spanning protein tyrosine kinase activity; protein binding; protein complex binding; protein-tyrosine kinase activity; receptor binding; signal transducer activity Biological Process: activation of JAK protein; adaptive immune response; angiogenesis; apoptosis; blood vessel endothelial cell migration; bone resorption; cell surface receptor linked signal transduction; cellular defense response; elevation of cytosolic calcium ion concentration; epidermal growth factor receptor signaling pathway; focal adhesion formation; glial cell proliferation; innate immune response; integrin-mediated signaling pathway; ionotropic glutamate receptor signaling pathway; MAPKKK cascade; marginal zone B cell differentiation; negative regulation of apoptosis; negative regulation of bone mineralization; negative regulation of cell proliferation; negative regulation of myeloid cell differentiation; negative regulation of neuron apoptosis; negative regulation of potassium ion transport; neurite development; oocyte maturation; peptidyl-tyrosine phosphorylation; positive regulation of actin filament polymerization; positive regulation of angiogenesis; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cell-matrix adhesion; positive regulation of JNK activity; positive regulation of JNK cascade; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase activity; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoinositide 3-kinase activity; positive regulation of protein kinase activity; positive regulation of synaptic transmission, glutamatergic; positive regulation of translation; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein complex assembly; regulation of calcium-mediated signaling; regulation of cell adhesion; regulation of cell shape; regulation of cGMP biosynthetic process; regulation of inositol trisphosphate biosynthetic process; regulation of release of sequestered calcium ion into cytosol; response to calcium ion; response to cAMP; response to cocaine; response to drug; response to ethanol; response to glucose stimulus; response to hormone stimulus; response to hydrogen peroxide; response to hypoxia; response to lithium ion; response to mechanical stimulus; response to osmotic stress; response to stress; signal complex assembly; signal transduction; sprouting angiogenesis; stress fiber formation; tumor necrosis factor-mediated signaling pathway; vascular endothelial growth factor receptor signaling pathway |
NCBI Summary: | This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008] |
UniProt Code: | Q14289 |
NCBI GenInfo Identifier: | 3183003 |
NCBI Gene ID: | 2185 |
NCBI Accession: | Q14289.2 |
UniProt Secondary Accession: | Q14289,Q13475, Q14290, Q16709, Q6PID4, D3DST0, |
UniProt Related Accession: | Q14289 |
Molecular Weight: | 111,183 Da |
NCBI Full Name: | Protein-tyrosine kinase 2-beta |
NCBI Synonym Full Names: | protein tyrosine kinase 2 beta |
NCBI Official Symbol: | PTK2B |
NCBI Official Synonym Symbols: | PKB; PTK; CAKB; FAK2; PYK2; CADTK; FADK2; RAFTK |
NCBI Protein Information: | protein-tyrosine kinase 2-beta |
UniProt Protein Name: | Protein-tyrosine kinase 2-beta |
UniProt Synonym Protein Names: | Calcium-dependent tyrosine kinase; CADTK; Calcium-regulated non-receptor proline-rich tyrosine kinase; Cell adhesion kinase beta; CAK-beta; CAKB; Focal adhesion kinase 2; FADK 2; Proline-rich tyrosine kinase 2; Related adhesion focal tyrosine kinase; RAFTK |
UniProt Gene Name: | PTK2B |
UniProt Entry Name: | FAK2_HUMAN |