BioPAX pathway converted from "PTK6 translocates to the nucleus" in the Reactome database. PTK6 translocates to the nucleus PTK6 translocates to the nucleus This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9709374 1 cytosol GO 0005829 UniProt:Q64434 Ptk6 Ptk6 Sik Ptk6 FUNCTION 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.ACTIVITY REGULATION Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity.SUBUNIT Interacts with KHDRBS1. Interacts with phosphorylated IRS4 (By similarity). Interacts with GAP-A.p65. Interacts with ADAM15 (By similarity). Interacts (via SH3 and SH2 domains) with phosphorylated IRS4 (By similarity). Interacts (via SH3 domain) with SFPQ (By similarity). Interacts with EGFR and ERBB2 (By similarity). Interacts with STAP2 (By similarity). Interacts with PNX (By similarity). Interacts with SFPQ (By similarity). Interacts with PTK/ATK (By similarity). Interacts with CTNNB1 (By similarity).TISSUE SPECIFICITY Expressed only in epithelial tissues, including the skin and lining of the alimentary canal. Restricted to the cell layers immediately above the proliferative cell zone in these epithelia.DEVELOPMENTAL STAGE First detected at day 15.5 of gestation in the embryo, where it is expressed in the newly forming granular layer of the skin. Is found in stomach at day 17.5.DOMAIN The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein-protein interactions, but is likely more important for the regulation of catalytic activity (By similarity).PTM Autophosphorylated. Autophosphorylation of Tyr-342 leads to an increase of kinase activity. Tyr-447 binds to the SH2 domain when phosphorylated and negatively regulates kinase activity (By similarity).DISRUPTION PHENOTYPE Deficient mice have an increased cell turnover in the small intestine, which is accompanied by increased villus length and crypt depth and delayed enterocyte differentiation that is accompanied by increased PTK/AKT and WNT signaling.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily. Reactome http://www.reactome.org Mus musculus NCBI Taxonomy 10090 UniProt Q64434 O4'-phospho-L-tyrosine at 342 342 EQUAL O4'-phospho-L-tyrosine [MOD:00048] Chain Coordinates 1 EQUAL 451 EQUAL Reactome DB_ID: 9907869 1 nucleoplasm GO 0005654 O4'-phospho-L-tyrosine at 342 342 EQUAL 1 EQUAL 451 EQUAL Reactome Database ID Release 82 9907871 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9907871 Reactome R-MMU-8848930 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8848930.1 PTK6 can localize to the nucleus. The mechanism of PTK6 (BRK) nuclear translocation is unknown (Derry et al. 2000). 10913193 Pubmed 2000 Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability Derry, J J Richard, S Valderrama Carvajal, H Ye, X Vasioukhin, V Cochrane, A W Chen, T Tyner, A L Mol. Cell. Biol. 20:6114-26 inferred by electronic annotation IEA GO IEA