PTK6
Description
The PTK6 (protein tyrosine kinase 6) is a protein-coding gene located on chromosome 20.
Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene. Tyrosine-protein kinase 6—also known as BRK (breast tumor kinase)—is a cytoplasmic non-receptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. The encoded protein has been shown to undergo autophosphorylation. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. PTK6 has been shown to interact with STAP2 and KHDRBS1.
PTK6, also known as Breast tumor kinase (BRK), is a non-receptor tyrosine-protein kinase involved in regulating various signaling pathways that control epithelial differentiation, maintenance, and tumor growth. Its function is context-dependent, varying based on cell type and intracellular localization. PTK6 has been shown to interact with a variety of proteins, including RNA-binding proteins (KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2, SFPQ/PSF), transcription factors (STAT3, STAT5A/B), and signaling molecules (ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS). It also interacts with proteins upstream of PTK6 in signaling pathways, like ADAM15, EGFR, ERBB2, ERBB3, and IRS4. In normal tissues, PTK6 promotes differentiation and apoptosis. However, in tumors, it contributes to cancer progression by sensitizing cells to mitogenic signals, enhancing proliferation, promoting anchorage-independent survival, and facilitating migration/invasion. PTK6's association with EGFR, ERBB2, and ERBB3 might contribute to mammary tumor development and growth by amplifying EGF-induced signaling through BTK/AKT and PI3 kinase. Furthermore, PTK6 contributes to migration and proliferation by mediating EGF-driven phosphorylation of ARHGAP35/p190RhoGAP, which in turn promotes association with RASA1/p120RasGAP, leading to RhoA inactivation and RAS activation. EGF stimulation also results in PTK6-mediated phosphorylation of PNX/Paxillin and subsequent activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to stimulate proliferation. Nuclear PTK6 might play a role in regulating growth in normal epithelia, while cytoplasmic PTK6 may activate oncogenic signaling pathways.
PTK6 is also known as BRK.
