| Function: |
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 s 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. |
| Tissue Specificity: |
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. |
| Sequence Similarities: |
Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. |
| Post-Translational Modification: |
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. |
| Cellular Location: |
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. |
| Database Links: |
Entrez Gene: 2185?HumanEntrez Gene: 19229?MouseEntrez Gene: 50646?RatOmim: 601212?HumanSwissProt: Q14289?HumanSwissProt: Q9QVP9?MouseSwissProt: P70600?RatUnigene: 491322?HumanUnigene: 21613?MouseUnigene: 11025?Rat |
| Synonyms: |
CADTK AntibodyCAK-beta AntibodyCAKB AntibodyCAKbeta AntibodyCalcium regulated non receptor proline rich tyrosine kinase AntibodyCalcium-dependent tyrosine kinase AntibodyCell adhesion kinase beta AntibodyE430023O05Rik AntibodyEC 2.7.10.2 AntibodyFADK 2 AntibodyFADK2 AntibodyFAK2 AntibodyFAK2_HUMAN AntibodyFocal adhesion kinase 2 AntibodyMGC124628 AntibodyPKB AntibodyProline-rich tyrosine kinase 2 AntibodyProtein kinase B AntibodyProtein Tyrosine Kinase 2 Beta AntibodyProtein-tyrosine kinase 2-beta AntibodyPTK AntibodyPTK2B AntibodyPTK2B protein tyrosine kinase 2 beta AntibodyPYK2 AntibodyRAFTK AntibodyRAFTK2 AntibodyRelated adhesion focal tyrosine kinase Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
