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FLASH GENE
Symbol MST1R contributors: mct/pgu - updated : 01-02-2015
HGNC name macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
HGNC id 7381
Location 3p21.2      Physical location : 49.924.437 - 49.941.306
Synonym name
  • RON protooncogene (Recepteur d'origine Nantais )
  • PTK8 protein tyrosine kinase 8
  • c-met-related tyrosine kinase
    • Synonym symbol(s) RON, CDW136, CDw136, PTK8, C-MET, METR
    EC.number 2.7.1.112
    DNA
    TYPE functioning gene
    STRUCTURE 16.87 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 4785 - 1400 - 2000 10959094
    - - 4638 - 1351 - 2000 10959094
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     stomach   highly
    Reproductivefemale systemuteruscervix highly
     male systemprostate  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticgranulocyte
    Blood/Hematopoieticmonocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal SEMA homology domain
  • a plexin homology domain
  • three IPT/TIG domains
  • a putative transmembrane segment (TM1)
  • a cytoplasmic tail with the kinase domain
  • two conserved tyrosine residues
  • C terminal SH2 binding sites
    • mono polymer heteromer , dimer
    isoforms Precursor precursor of 180kDa cleaved into a 40kDa alpha chain and a 145kDa beta chain
    HOMOLOGY
    intraspecies homolog to stem cell tyrosine kinase receptor (Stk)
    homolog to hepacyte growth factor receptor (MET)
    Homologene
    FAMILY MET family , tyr protein kinase family
    CATEGORY protooncogene , receptor tyrosine kinase
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • involved in development of epithelial tissue (early embryonic period)
  • is involved in cell proliferation, cell survival, and cell motility in both normal and disease states
  • has a tyrosine-protein kinase activity
  • playing an important role for cell proliferation, differentiation, and cancer development
  • regulates both the production of and response to IFN-gamma, resulting in enhanced susceptibility to endotoxin challenge
  • may have has two alternative modes of signaling that can contribute to oncogenic behavior in normal breast epithelial cells
  • potentially involved in mesangial cell proliferation under both physiological and pathological conditions, and may be a relevant target for therapeutic intervention
  • plays a critical role in regulation of alveolar macrophage signaling
  • important in modulating prostate tumor growth by modulating angiogenic chemokine production and subsequent endothelial cell recruitment
  • in a complex with EGFR, acts as a transcriptional regulator in response to acute disturbances (serum starvation) imposed on cancer cells
    • . MST1/MST1R signaling seems to play at least some role in the pathogenesis of Merkel cell carcinoma
  • MST1/MST1R play important roles in inflammation, cell growth, migration, and epithelial to mesenchymal transition during tumor development
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer formed of an alpha chain and a beta chain which are disulfide linked
  • MST1/MST1R system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • receptor for macrophage stimulating protein (MST1)
  • binds PLXNB1
  • associates with and is negatively regulated by HYAL2
  • downstream target of the EPOR, involved in the expansion of erythroblasts
  • DNAJA3 binds to unphosphorylated MST1R and becomes dissociated from the receptor upon HGF stimulation
  • DNAJA3(S) or Tid-1(S) is an essential regulatory component of MST1R signaling
  • CTNNB is a crucial downstream regulator of MST1R activation and is an important mediator of mammary tumorigenesis
  • TMPRSS11D is likely important for MST1-MST1R signaling in the respiratory tract
  • SRSF2 promotes exon 11 inclusion of MST1R proto-oncogene through targeting exon 11
  • MST1 through binding to its receptor, RON or MST1R), it can activate epithelial cells and work as an inflammatory mediator
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in the invasive phenotype of colorectal carcinomas
    tumoral       gain of function
    in lung carcinoma
    constitutional     --over  
    can inhibit cell proliferation and induce senescence
    tumoral     --over  
    in hypopharyngeal squamous cell carcinoma
    tumoral     --over  
    in a significant number of breast cancer tissues as well as in many established breast cancer cell lines
    tumoral     --over  
    frequently overexpressed and constitutively phosphorylated in a number of human malignancies
    Susceptibility
    Variant & Polymorphism insertion/deletion , other splicing variant of 160kDa cleaved into an alpha 40kDa chain a 125kDa beta chain resulting from a 109AA deletion of the extracellular domain, in colorectal carcinomas
    Candidate gene
    Marker
  • novel prognostic marker and therapeutic target for gastroesophageal cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    malignant glioma could represent candidate targets for treatment with agents inhibiting MST1R activity
    cancerhemopathy 
    may be a novel therapeutic target for EBV-associated lymphoproliferative diseases
    ANIMAL & CELL MODELS
    conferring susceptibility to friend virus induced erythroleukemia in mice