Hepatocyte Growth Factor Receptor Signaling Pathway BioCarta

Preferred Label : Hepatocyte Growth Factor Receptor Signaling Pathway BioCarta;

NCIt synonyms : Hepatocyte Growth Factor Receptor Signaling Pathway;

NCIt related terms : Signaling of Hepatocyte Growth Factor Receptor;

Alternative definition : BIOCARTA: The hepatocyte growth factor receptor, also called c-Met, is activated by HGF and stimulates proliferation of hepatocytes and other cell types. Mutated forms of the HGF receptor are associated with oncogenesis and metastasis, making the HGF receptor a potential therapeutic target for cancer drugs. Changes in cell motility, cell shape, adhesion, resistance to apoptosis, and anchorage independent growth all contribute to the role of c-Met in cancer. The HGF receptor is a heterodimer with tyrosine kinase activity and associates with a multiprotein complex involved in downstream signal transduction. The HGF receptor can associate with several different signaling systems, including src, Grb2/SOS, PI3 kinase and Gab1. One of the major substrates of the activated HGF receptor tyrosine kinase is the adaptor protein Gab1. Gab1 interacts with Crk and CrkL, two proteins with SH2 and SH3 protein interaction domains that couple to signaling further downstream. The actions of HGF on paxillin, DOCK180, and Rap1, mediated through GAB1 and other members of this complex, alter cell motility. Regulation of Rho, Rac1, and CDC42 pathways in response to HGF all contribute to changes in cellular motility. Another target of the HGF receptor kinase is the focal adhesion kinase, FAK. The activation of FAK induces the formation of focal adhesions, a preliminary step to increased cell motility and tissue invasion by transformed cells, and paxillin phosphorylation may also alter cell adhesion of Met transformed cells. Src and p130cas are required for the role of FAK in HGF induced cellular transformation. HGF also blocks anoikis, the induction of apoptosis through suspension of cells, by acting on Erk and AKT kinases. This activity may contribute to anchorage independent growth of Met transformed cells. Signaling by integrins also plays a key role in the activation of tissue invasive growth by HGF. The alpha6beta4 integrin acts as a cofactor along with Meta to participate in cell growth and proliferation. In addition to altering cell adhesion, proliferation, and cell motility, HGF alters cellular transcription through activation of STAT3. STAT3 activation by HGF is independent of PI3 kinase or map kinases and alters gene expression leading to changes in cellular shape. Although HGF is associated with cellular proliferation and survival, in rat liver epithelial cells HGF induces apoptosis and inhibits cell growth. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

NCI Metathesaurus CUI : CL437115;

Biocarta ID : h_metPathway;

Details

Origin ID

C39152;

UMLS CUI

C1155393;

Automatic exact mappings (from CISMeF team)
- hepatocyte growth factor receptor signaling pathway [GO term]
Semantic type(s)
- Molecular Function [UMLS semantic type]
UMLS correspondences (same concept)
- hepatocyte growth factor receptor signaling pathway [GO term]
has_gene_product_element
- Adapter Molecule crk [NCIt concept]
- Crk-Like Protein [NCIt concept]
- Dedicator of Cytokinesis Protein 1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- ETS Domain-Containing Protein Elk-1 [NCIt concept]
- Focal Adhesion Kinase 1 [NCIt concept]
- GRB2-Associated-Binding Protein 1 [NCIt concept]
- GTPase HRas [NCIt concept]
- Growth Factor Receptor-Bound Protein 2 [NCIt concept]
- Hepatocyte Growth Factor [NCIt concept]
- Hepatocyte Growth Factor Receptor [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 [NCIt concept]
- Phosphatidylinositol 3,4,5-Trisphosphate 3-Phosphatase and Dual-Specificity Protein Phosphatase PTEN [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- Protein-Tyrosine Kinase 2-Beta [NCIt concept]
- Proto-Oncogene Tyrosine-Protein Kinase Src [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- RAS-Related Protein Rap-1A [NCIt concept]
- Rap Guanine Nucleotide Exchange Factor 1 [NCIt concept]
- Signal Transducer and Activator of Transcription 3 [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Tyrosine-Protein Phosphatase Non-Receptor Type 11 [NCIt concept]
pathway_has_gene_element
- CRK wt Allele [NCIt concept]
- CRKL wt Allele [NCIt concept]
- DOCK1 wt Allele [NCIt concept]
- ELK1 wt Allele [NCIt concept]
- GAB1 wt Allele [NCIt concept]
- GRB2 wt Allele [NCIt concept]
- HGF wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MAP4K1 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- MET wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PTEN wt Allele [NCIt concept]
- PTK2 wt Allele [NCIt concept]
- PTK2B wt Allele [NCIt concept]
- PTPN11 wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- RAP1A wt Allele [NCIt concept]
- RAPGEF1 wt Allele [NCIt concept]
- SRC wt Allele [NCIt concept]
- STAT3 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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