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FLASH GENE
Symbol PTK6 contributors: mct/ - updated : 07-04-2015
HGNC name PTK6 protein tyrosine kinase 6
HGNC id 9617
Location 20q13.33      Physical location : 62.159.777 - 62.168.707
Synonym name
  • protein tyrosine kinase, non receptor type
  • breast tumor kinase
  • protein-tyrosine kinase BRK
    • Synonym symbol(s) BRK, FLJ42088
    EC.number 2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 8.96 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - codon stop - - - brain 2011 21479203
  • truncated form
  • lacking the SH2 domain
  • a novel proline rich C terminus expression
    • - splicing 2413 - 134 - 2011 21479203
  • also called ALT-PTK6, or lambdaM5
  • catalytically inactive splice variant
  • alternative transcript, which shares the first 77 amino acid including the SH3 domain with full length PTK6
  • is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization
    • 8 - 2519 - 451 - 2011 21479203
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel     Homo sapiens
    Digestiveesophagus   highly
     intestinelarge intestine   
     mouthtongue  highly
    Reproductivefemale systembreast  highly Homo sapiens
     male systemprostate    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines human breast carcinoma cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a SH3 domain interacting with the N-terminal half of the linker (Linker) region between the SH2 and kinase domains
  • a SH2 domain
  • a tyrosine kinase catalytic (kinase) domain
    • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • BRK/PTK6/SIK subfamily
    • CATEGORY transcription factor , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    text
  • localization of PTK6 to the plasma membrane enhanced the ability of PTK6 to promote proliferation, cell survival and migration and to permit anchorage-independent colony formation, but nuclear localization of PTK6 impaired these functions
  • localizes to the nuclei of normal prostate epithelial cells, but becomes cytoplasmic in human prostate tumors
    • basic FUNCTION
  • may be functioning as an intracellular signal transducer in epithelial tissues
  • promotes cell migration and tumor invasion by phosphorylating the focal adhesion protein paxillin
  • phosphorylates GRLF1 at the Y(1105) residue, thereby promoting the association of GRLF1 with RASA1
  • having a function in regulating both RHOA and RAS by phosphorylating GRLF1 and provide evidence for the crucial roles of this PTK6-elicited signaling pathway in promoting breast malignancy
  • enhances breast carcinoma cell survival in suspension, suggesting a role for TRK6 in supporting breast cancer cell dissemination
  • recruitment of PTK6 to the plasma membrane is required for oncogenic function
  • both FRK and PTK6 have been implicated in the regulation of epithelial cell differentiation and apoptosis
  • PTK6 negatively regulates AKT signaling in normal tissues, and it may enhance AKT signaling in breast cancer cells
  • ability to negatively regulate CTNNB1/TCF transcription by modulating levels of TCF4 and TLE/Groucho could contribute to its growth-inhibitory activities
  • nonmyristoylated Src-related intracellular tyrosine kinase, phosphorylating AKT1 in a Src family kinase-independent manner
  • enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells
  • function in cell-type and context-dependent processes governing normal differentiation
  • phosphorylating regulatory RNA-binding proteins, adaptor molecules that link PTK6 to signaling pathways generally associated with the activation of growth factor receptors, and Signal Transducers and Activators of Transcription (STAT) molecules that are direct regulators of gene expression
  • plays a functional role in the differentiation of the keratinocytes in the epidermis
  • previously unknown role of PTK6 in EGFR-targeted therapy
  • important roles for a PTK6-PTK2-AKT1 signaling axis in promoting anchorage-independent cell survival
  • intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth
  • novel functions for PTK6 in the pathophysiology of prostate cancer
  • novel mechanism of action of PTK6 in the promotion of tumor formation, which involves the targeting of tumor suppressor DOK1 for degradation through the ubiquitin proteasomal pathway
  • regulates cellular migration and invasion in pancreatic cancer via ERK signaling
  • participates in regulating epithelial barrier function, and role of PTK6 in mediating endothelial barrier dysfunction
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • PTK6-BCAR1-MAPK7 signaling cascade plays an important role in cancer cell migration and invasion
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associates with IRS4 in resting and insulin-like growth factor 1 (IGF1)
  • targets the SFPQ RNA-binding protein during EGF stimulation
  • associates with nuclear and cytoplasmic beta-catenin and inhibits beta-catenin- and T-cell factor (TCF)-mediated transcription
  • association with AKT1 occuring through the SH3 domain of PTK6 and is enhanced through SH2 domain-mediated interactions following tyrosine phosphorylation of AKT1
  • STAP2 upregulated PTK6-mediated activation of STAT3 in breast cancer cells
  • BCAR1 is a novel direct substrate of PTK6, and it works as a crucial adapter protein in inducing peripheral adhesion complexes
  • PTK6, a nonreceptor protein-tyrosine kinase highly expressed in most human breast tumors, interacted with EGFR and sustained ligand-induced EGFR signaling
  • phosphorylates and down-regulates E3 ubiquitin ligase CBL, promoting degradation of CBL through PTK6-mediated phosphorylation
  • RPS6KA1 regulates anchorage-independent growth through transcriptional regulation of factors that modulate cell survival, including ING3, CKAP2, and PTK6
  • contributes to vascular endothelial hyperpermeability in response to TNF
  • plasma-membrane-associated PTK6 phosphorylates EPS8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic breast cancer and in breast carcinoma cell lines
    tumoral       gain of function
    plays a role in cell proliferation and tumorigenesis in breast cancer cells and tissues
    tumoral       gain of function
    retention of PTK6 in the cytoplasm of prostate cancer cells disrupts its ability to regulate nuclear substrates and leads to aberrant growth
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinepancreas
    may be a novel therapeutic target for pancreatic cancer
    cancerreproductiveprostate
    in prostate cancer, restoring PTK6 nuclear localization may have therapeutic advantages
    ANIMAL & CELL MODELS