Activating Compound | Comment | Organism | Structure |
---|---|---|---|
heregulin | ligand for the Met receptor | Mus musculus | |
heregulin | loss of tyrosine phosphorylation of the receptor is detectable as early as 15 min post-chase, whereas Met itself is stable, demonstrating that under these conditions Met is significantly dephosphorylated prior to degradation | Homo sapiens | |
additional information | Met tyrosine phosphorylation is elevated in cells in which the levels of either PTP1B or TCPTP are knocked down by specific siRNA, but not in cells transfected with scrambled siRNA. When both PTP1B and TCPTP are targeted together, up to 3fold higher tyrosine phosphorylation of Met is observed, suggesting an additive role for these phosphatases in the regulation of tyrosine phosphorylation of Met | Homo sapiens |
Application | Comment | Organism |
---|---|---|
additional information | PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor tyrosine kinase. Residues Y1234 and Y1235 of Met are essential for the interaction of Met with TCPTP and PTP1B, while Y1003 may play an accessory role | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
K1110A | dead Met kinase, present at the plasma membrane | Homo sapiens |
Y1003F | coimmunoprecipitates with D/A mutants of PTP1B and TCPTP, although the interaction is decreased when compared to wild-type Met with TCPTP | Homo sapiens |
Y1234/Y1235F | substitution of both tyrosine residues additionally decreases the ability of both TCPTP (D/A) and PTP1B (D/A) mutants to coimmunoprecipitate with Met | Homo sapiens |
Y1234F | coimmunoprecipitation of tyrosine-phosphorylated Met with TCPTP (D/A) or PTP1B (D/A) decreases significantly | Homo sapiens |
Y123F | coimmunoprecipitation of tyrosine-phosphorylated Met with TCPTP (D/A) or PTP1B (D/A) decreases significantly | Homo sapiens |
Y1349F | no significant decrease in the ability of PTP1B D/A or TCPTP D/A mutants to coimmunoprecipitate | Homo sapiens |
Y1349F/Y1356F | no significant decrease in the ability of PTP1B D/A or TCPTP D/A mutants to coimmunoprecipitate | Homo sapiens |
Y1356F | no significant decrease in the ability of PTP1B D/A or TCPTP D/A mutants to coimmunoprecipitate | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
cycloheximide | depletes the synthetic pool of Met receptor | Homo sapiens | |
protein tyrosine phosphatase 1B | PTP1B, requirement for Y1234 and Y1235 in the Met receptor activation loop for interaction with PTP1B | Homo sapiens | |
protein tyrosine phosphatase 1B | PTP1B, negative regulator of Met. Loss of protein tyrosine phosphatase 1B enhances heregulin-mediated phosphorylation of Met. Interaction with Met requires phosphorylation of twin tyrosines (Y1234/35) in the activation loop of the Met kinase domain | Mus musculus | |
T-cell phosphatase | TCPTP, requirement for Y1234 and Y1235 in the Met receptor activation loop for interaction with TCPTP | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | active Met | Homo sapiens | 5737 | - |
additional information | in the absence of heregulin, localization of PTP1B D/A, but not wild-type PTP1B with endogenous Met receptor in a perinuclear structure. Stimulation with heregulin, PTP1B D/A, but not cells overexpressing PTP1B wild-type is present in peripheral puncta with the Met receptor at 5' post-stimulation. Trapping mutants of both PTP1B and the ER-targeted TCPTP isoform, TC48, colocalize with Met. Activation of Met enables the nuclear-localized isoform of TCPTP, TC45, to exit the nucleus | Homo sapiens | - |
- |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HeLa cell | - |
Homo sapiens | - |
liver | - |
Mus musculus | - |
Synonyms | Comment | Organism |
---|---|---|
hepatocyte growth factor receptor | - |
Mus musculus |
hepatocyte growth factor receptor | - |
Homo sapiens |
MET | - |
Mus musculus |
MET | - |
Homo sapiens |
Met receptor-tyrosine kinase | - |
Mus musculus |
Met receptor-tyrosine kinase | - |
Homo sapiens |
Met RTK | - |
Mus musculus |
Met RTK | - |
Homo sapiens |