Protein-tyrosine kinase 6 (EC 2.7.10.2) (Breast tumor kinase) (Tyrosine-protein kinase BRK)
1_MVSRD 6_ QAHLG 11_ PKYVG 16_ LWDFK 21_ SRTDE 26_ ELSFR 31_ AGDVF 36_ HVARK 41_ EEQWW 46_ WATLL 51_ DEAGG 56_ AVAQG 61_ YVPHN 66_ YLAER 71_ ETVES 76_ EPWFF 81_ GCISR 86_ SEAVR 91_ RLQAE 96_ GNATG 101_ AFLIR 106_ VSEKP 111_ SADYV 116_ LSVRD 121_ TQAVR 126_ HYKIW 131_ RRAGG 136_ RLHLN 141_ EAVSF 146_ LSLPE 151_ LVNYH 156_ RAQSL 161_ SHGLR 166_ LAAPC 171_ RKHEP 176_ EPLPH 181_ WDDWE 186_ RPREE 191_ FTLCR 196_ KLGSG 201_ YFGEV 206_ FEGLW 211_ KDRVQ 216_ VAIKV 221_ ISRDN 226_ LLHQQ 231_ MLQSE 236_ IQAMK 241_ KLRHK 246_ HILAL 251_ YAVVS 256_ VGDPV 261_ YIITE 266_ LMAKG 271_ SLLEL 276_ LRDSD 281_ EKVLP 286_ VSELL 291_ DIAWQ 296_ VAEGM 301_ CYLES 306_ QNYIH 311_ RDLAA 316_ RNILV 321_ GENTL 326_ CKVGD 331_ FGLAR 336_ LIKED 341_ VYLSH 346_ DHNIP 351_ YKWTA 356_ PEALS 361_ RGHYS 366_ TKSDV 371_ WSFGI 376_ LLHEM 381_ FSRGQ 386_ VPYPG 391_ MSNHE 396_ AFLRV 401_ DAGYR 406_ MPCPL 411_ ECPPS 416_ VHKLM 421_ LTCWC 426_ RDPEQ 431_ RPCFK 436_ ALRER 441_ LSSFT 446_SYENP
1: 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. Phosphorylates the GTPase-activating protein ARAP1 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation (PubMed:20554524). Also associates 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
2: Inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins