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Literature summary for 2.7.10.1 extracted from

  • Sangwan, V.; Paliouras, G.N.; Abella, J.V.; Dube, N.; Monast, A.; Tremblay, M.L.; Park, M.
    Regulation of the Met receptor tyrosine kinase by the protein tyrosine phosphatases PTP1B and TCPTP (2008), J. Biol. Chem., 283, 34374-34383.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.10.1

Activating Compound

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

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

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

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

Localization Comment Organism GeneOntology No. Textmining
cytoplasm active Met Homo sapiens 5737
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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
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Organism

Organism UniProt Comment Textmining
Homo sapiens
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Mus musculus
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Source Tissue

Source Tissue Comment Organism Textmining
HeLa cell
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 Homo sapiens
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liver
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 Mus musculus
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Synonyms

Synonyms Comment Organism
hepatocyte growth factor receptor
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 Mus musculus
hepatocyte growth factor receptor
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 Homo sapiens
MET
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 Mus musculus
MET
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 Homo sapiens
Met receptor-tyrosine kinase
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 Mus musculus
Met receptor-tyrosine kinase
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 Homo sapiens
Met RTK
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 Mus musculus
Met RTK
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 Homo sapiens