Brk
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways. Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily. Epithelia-specific. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues. Not expressed in breast or ovarian tissue but expressed in high percentage of breast and ovarian cancers. Also overexpressed in some metastatic melanomas, lymphomas, colon cancers, squamous cell carcinomas and prostate cancers. Also found in melanocytes. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 2 is present in prostate epithelial cell lines derived from normal prostate and prostate adenocarcinomas, as well as in a variety of cell lines. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.2; Kinase, protein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); SRM subfamily; Src family; TK group
Cellular Component: cytoplasm; cytosol; extrinsic component of cytoplasmic side of plasma membrane; nuclear body; nucleoplasm; nucleus; plasma membrane; ruffle
Molecular Function: ATP binding; identical protein binding; non-membrane spanning protein tyrosine kinase activity; protein binding; protein tyrosine kinase activity; signaling receptor binding
Biological Process: cell differentiation; cell migration; cellular response to retinoic acid; ERBB2 signaling pathway; innate immune response; intestinal epithelial cell differentiation; negative regulation of growth; negative regulation of protein tyrosine kinase activity; positive regulation of cell cycle; positive regulation of epidermal growth factor receptor signaling pathway; positive regulation of neuron projection development; positive regulation of tyrosine phosphorylation of STAT protein; protein autophosphorylation; protein phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; tyrosine phosphorylation of STAT protein