PTK2B
Description
The PTK2B (protein tyrosine kinase 2 beta) is a protein-coding gene located on chromosome 8.
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.
== Function == This gene encodes a cytoplasmic protein tyrosine kinase that 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. In addition, SOCE-induced Pyk2 activation mediates disassembly of endothelial adherens junctions, via tyrosine (Y1981-residue) phosphorylation of VE-PTP. This protein has been shown to bind a CRK-associated substrate, a nephrocystin, a 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.
PTK2B, also known as PYK2, is a non-receptor protein tyrosine kinase that plays a crucial role in regulating various cellular processes, including actin cytoskeleton reorganization, cell polarization, migration, adhesion, spreading, and bone remodeling. It is involved in the regulation of the humoral immune response, influencing the levels of marginal B-cells in the spleen and the migration of splenic B-cells. PTK2B is also essential for normal macrophage polarization and migration to inflammatory sites. It regulates cytoskeletal rearrangement and cell spreading in T-cells, contributing to the regulation of T-cell responses. PTK2B promotes osteoclastic bone resorption, a process that requires both PTK2B/PYK2 and SRC. It may also inhibit the differentiation and activity of osteoprogenitor cells. PTK2B functions in signaling pathways downstream of various receptors, including integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates cellular responses to stress. Upon activation, PTK2B forms multisubunit signaling complexes with SRC and SRC family members, leading to the phosphorylation of additional tyrosine residues. These phosphorylated residues serve as binding sites for scaffold proteins, effectors, and substrates, allowing PTK2B to regulate numerous signaling pathways. PTK2B promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade, as well as the activation of NOS3, regulating the production of the cellular messenger cGMP. It also promotes the activation of the MAP kinase signaling cascade, including the activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. PTK2B further promotes the activation of Rho family GTPases, such as RHOA and RAC1. It recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, regulating P53/TP53 activity, ubiquitination, and proteasomal degradation. PTK2B acts as a scaffold, binding to both PDPK1 and SRC, allowing SRC to phosphorylate PDPK1 at 'Tyr-9', 'Tyr-373', and 'Tyr-376'. It promotes the phosphorylation of NMDA receptors by SRC family members, contributing to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. PTK2B may also regulate potassium ion transport by phosphorylation of potassium channel subunits. PTK2B phosphorylates SRC, increasing SRC kinase activity, and also phosphorylates ASAP1, NPHP1, KCNA2, and SHC1. It promotes the phosphorylation of ASAP2, RHOU, and PXN, a process that requires both SRC and PTK2/PYK2. PTK2B exists as a homodimer or homooligomer, and interacts with various proteins, including SIRPA, SH2D3C, ARHGAP10, DLG4, KCNA2, NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2, TGFB1I1, SRC (via SH2 domain), EPHA1, LCK, phosphatidylinositol 3-kinase, GRB2 (via SH2 domain), P53/TP53, MDM2, MYLK, BCAR1, PDPK1, PXN, RB1CC1, RHOU, VAV1, LPXN, and PTPN12.
PTK2B is also known as CADTK, CAKB, FADK2, FAK2, PKB, PTK, PYK2, RAFTK.
