PTK2B

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]

PTK2B

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.

Activation of GTPase activityIEA:Ensembl
Activation of Janus kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Adaptive immune responseIEA:UniProtKB-KW
Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Blood vessel endothelial cell migrationIEA:Ensembl
Bone resorptionISS:UniProtKB
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell surface receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Cellular defense responseISS:Alzheimers_University_of_Toronto
Cellular response to fluid shear stressIEA:Ensembl
Cellular response to retinoic acidManual Assertion Based On ExperimentIMP:BHF-UCL
Chemokine-mediated signaling pathwayISS:UniProtKB
Endothelin receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Epidermal growth factor receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Focal adhesion assemblyIEA:Ensembl
Glial cell proliferationIEA:Ensembl
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Ionotropic glutamate receptor signaling pathwayISS:Alzheimers_University_of_Toronto
Long-term synaptic depressionIEA:Ensembl
Long-term synaptic potentiationISS:Alzheimers_University_of_Toronto
MAPK cascadeIEA:Ensembl
Marginal zone B cell differentiationISS:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of bone mineralizationISS:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of muscle cell apoptotic processIEA:Ensembl
Negative regulation of myeloid cell differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of neuron apoptotic processISS:Alzheimers_University_of_Toronto
Negative regulation of potassium ion transportManual Assertion Based On ExperimentIDA:UniProtKB
Neuron projection developmentIEA:Ensembl
Oocyte maturationIEA:Ensembl
Peptidyl-tyrosine autophosphorylationManual Assertion Based On ExperimentIDA:CACAO
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of actin filament polymerizationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of angiogenesisIEA:Ensembl
Positive regulation of B cell chemotaxisISS:UniProtKB
Positive regulation of cell growthIEA:Ensembl
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell-matrix adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cytosolic calcium ion concentrationIEA:Ensembl
Positive regulation of DNA biosynthetic processIEA:Ensembl
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of excitatory postsynaptic potentialISS:Alzheimers_University_of_Toronto
Positive regulation of JNK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JUN kinase activityIEA:Ensembl
Positive regulation of neuron projection developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of nitric oxide biosynthetic processIEA:Ensembl
Positive regulation of nitric-oxide synthase activityIEA:Ensembl
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase activityISS:UniProtKB
Positive regulation of protein kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of reactive oxygen species metabolic processIEA:Ensembl
Positive regulation of synaptic transmission, glutamatergicISS:Alzheimers_University_of_Toronto
Positive regulation of translationIEA:Ensembl
Positive regulation of ubiquitin-dependent protein catabolic processIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentTAS:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Protein-containing complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Regulation of actin cytoskeleton reorganizationISS:UniProtKB
Regulation of calcium-mediated signalingIEA:Ensembl
Regulation of cell adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell shapeManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cGMP-mediated signalingIEA:Ensembl
Regulation of establishment of cell polarityISS:UniProtKB
Regulation of inositol trisphosphate biosynthetic processISS:UniProtKB
Regulation of macrophage chemotaxisISS:UniProtKB
Regulation of NMDA receptor activityISS:Alzheimers_University_of_Toronto
Regulation of release of sequestered calcium ion into cytosolISS:UniProtKB
Regulation of synaptic plasticityManual Assertion Based On ExperimentTAS:ARUK-UCL
Regulation of ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Response to calcium ionIEA:Ensembl
Response to cAMPIEA:Ensembl
Response to cation stressIEA:Ensembl
Response to cocaineIEA:Ensembl
Response to ethanolIEA:Ensembl
Response to glucoseIEA:Ensembl
Response to hormoneIEA:Ensembl
Response to hydrogen peroxideIEA:Ensembl
Response to hypoxiaIEA:Ensembl
Response to immobilization stressIEA:Ensembl
Response to ischemiaIEA:Ensembl
Response to lithium ionIEA:Ensembl
Response to mechanical stimulusIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Sprouting angiogenesisISS:UniProtKB
Stress fiber assemblyIEA:Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL

Cytoplasm
Cytoplasm, perinuclear region
Cell membrane
Cell junction, focal adhesion
Cell projection, lamellipodium
Cytoplasm, cell cortex
Nucleus
Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with integrins at the cell periphery.

Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.

Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12.