Search results for MET

Showing 19 results out of 753

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (2 results from a total of 32)

MET

Identifier: R-HSA-419603
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: MET: P08581
Identifier: R-HSA-6807014
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: MET: P08581

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9005531
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000105976

Pathway (2 results from a total of 158)

Identifier: R-HSA-6806834
Species: Homo sapiens
MET is a receptor tyrosine kinase (RTK) (Cooper et al. 1984, Park et al. 1984) activated by binding to its ligand, Hepatocyte growth factor/Scatter factor (HGF/SF) (Bottaro et al. 1991, Naldini et al. 1991). Similar to other related RTKs, such as EGFR, ligand binding induces MET dimerization and trans-autophosphorylation, resulting in the active MET receptor complex (Ferracini et al. 1991, Longati et al. 1994, Rodrigues and Park 1994, Kirchhofer et al. 2004, Stamos et al. 2004, Hays and Watowich 2004). Phosphorylated tyrosines in the cytoplasmic tail of MET serve as docking sites for binding of adapter proteins, such as GRB2, SHC1 and GAB1, which trigger signal transduction cascades that activate PI3K/AKT, RAS, STAT3, PTK2, RAC1 and RAP1 signaling (Ponzetto et al. 1994, Pelicci et al. 1995, Weidner et al. 1995, Besser et al. 1997, Shen and Novak 1997, Beviglia and Kramer 1999, Rodrigues et al. 2000, Sakkab et al. 2000, Schaeper et al. 2000, Lamorte et al. 2002, Wang et al. 2002, Chen and Chen 2006, Palamidessi et al. 2008, Chen et al. 2011, Murray et al. 2014).
Activation of PLC gamma 1 (PLCG1) signaling by MET remains unclear. It has been reported that PLCG1 can bind to MET directly (Ponzetto et al. 1994) or be recruited by phosphorylated GAB1 (Gual et al. 2000). Tyrosine residue Y307 of GAB1 that serves as docking sites for PLCG1 may be phosphorylated either by activated MET (Watanabe et al. 2006) or SRC (Chan et al. 2010). Another PCLG1 docking site on GAB1, tyrosine residue Y373, was reported as the SRC target, while the kinase for the main PLCG1 docking site, Y407 of GAB1, is not known (Chan et al. 2010).
Signaling by MET promotes cell growth, cell survival and motility, which are essential for embryonic development (Weidner et al. 1993, Schmidt et al. 1995, Uehara et al. 1995, Bladt et al. 1995, Maina et al. 1997, Maina et al. 2001, Helmbacher et al. 2003) and tissue regeneration (Huh et al. 2004, Borowiak et al. 2004, Liu 2004, Chmielowiec et al. 2007). MET signaling is frequently aberrantly activated in cancer, through MET overexpression or activating MET mutations (Schmidt et al. 1997, Pennacchietti et al. 2003, Smolen et al. 2006, Bertotti et al. 2009).
Considerable progress has recently been made in the development of HGF-MET inhibitors in cancer therapy. These include inhibitors of HGF activators, HGF inhibitors and MET antagonists, which are protein therapeutics that act outside the cell. Kinase inhibitors function inside the cell and have constituted the largest effort towards MET-based therapeutics (Gherardi et al. 2012).
Pathogenic bacteria of the species Listeria monocytogenes, exploit MET receptor as an entryway to host cells (Shen et al. 2000, Veiga and Cossart 2005, Neimann et al. 2007).
For review of MET signaling, please refer to Birchmeier et al. 2003, Trusolino et al. 2010, Gherardi et al. 2012, Petrini 2015.
Identifier: R-HSA-6807004
Species: Homo sapiens
Signaling by MET receptor is negatively regulated mainly by MET receptor dephosphorylation or MET receptor degradation. Protein tyrosine phosphatase PTPRJ dephosphorylates MET tyrosine residue Y1349, thus removing the docking site for the GAB1 adapter (Palka et al. 2003). Protein tyrosine phosphatases PTPN1 and PTPN2 dephosphorylate MET tyrosines Y1234 and Y1235 in the kinase activation loop, thus attenuating catalytic activity of MET (Sangwan et al. 2008). The E3 ubiquitin ligase CBL promotes ubiquitination of the activated MET receptor and subsequent MET degradation. CBL contains a RING finger domain that engages E2 protein ubiquitin ligases to mediate ubiquitination of MET, which may occur at the cell membrane or in the early endocytic compartment. Ubiquitinated MET is degraded in a late endosomal or lysosomal compartment in a proteasome-dependent manner. The involvement of proteasome in MET degradation seems to be indirect, through an effect on MET endocytic trafficking (Jeffers et al. 1997, Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002). LRIG1 promotes lysosome-dependent degradation of MET in the absence of HGF-mediated activation (Lee et al. 2014, Oh et al. 2014).
MET-mediated activation of RAS signaling is inhibited by MET receptor binding to MUC20 (Higuchi et al. 2004) or RANBP10 (Wang et al. 2004).

Complex (2 results from a total of 98)

Identifier: R-HSA-9658856
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-8851839
Species: Homo sapiens
Compartment: plasma membrane

RNA Sequence (2 results from a total of 10)

Identifier: R-HSA-9708205
Species: Homo sapiens
Compartment: cytosol
Primary external reference: RNAcentral: tRNA Met CAT: URS0000145C5E_9606
Identifier: R-HSA-9708360
Species: Homo sapiens
Compartment: cytosol
Primary external reference: RNAcentral: URS0000145C5E_9606

Reaction (2 results from a total of 320)

Identifier: R-HSA-8875374
Species: Homo sapiens
Compartment: plasma membrane
LRIG1 can bind the MET receptor in the absence of HGF-mediated MET activation and trigger MET downregulation in a CBL-independent manner (Shattuck et al. 2007). MET targeting by the therapeutic antibody SAIT301 leads to LRIG1-mediated MET degradation through the lysosomal route. LRIG1-mediated MET downregulation requires ubiquitination of LRIG1 by an unknown ubiquitin ligase and can be inhibited by the ubiqitin hydrolase USP8, which deubiquitinates LRIG1 (Oh et al. 2014, Lee et al. 2014). Ubiquitinated LRIG1 binds to HGS (Hrs), a protein involved in clathrin-mediated endocytosis, and LRIG1 and MET co-localize with the lysosomal marker LAMP1 (Oh et al. 2014).
Identifier: R-HSA-8851866
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The sprouty (SPRY) domain of RANBP10 binds the tyrosine kinase domain of MET. RANBP10 binding inhibits binding of RANBP9 to MET and, as RANBP10 does not interact with SOS1, RANBP10 binding interferes with RAS activation (Wang et al. 2004).

Chemical Compound (2 results from a total of 30)

Identifier: R-ALL-174390
Compartment: cytosol
Primary external reference: ChEBI: L-methionine zwitterion: 57844
Identifier: R-ALL-379705
Compartment: mitochondrial matrix
Primary external reference: ChEBI: L-methionine zwitterion: 57844

Genes and Transcripts (2 results from a total of 34)

Identifier: R-HSA-379794
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-379780
Species: Homo sapiens
Compartment: mitochondrial matrix

OtherEntity (2 results from a total of 10)

Identifier: R-ALL-72393
Compartment: cytosol
Identifier: R-ALL-1222500
Compartment: cytosol

Set (2 results from a total of 20)

Identifier: R-HSA-8851934
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-8876353
Species: Homo sapiens
Compartment: plasma membrane
Cite Us!