ArticleOncogene1999
Activating mutations in the Met receptor overcome the requirement for autophosphorylation of tyrosines crucial for wild type signaling.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Autoregulation of the MET receptor tyrosine kinase by its intracellular juxtamembrane domain.The Biochemical journal · 2025Article
- MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation.Molecular oncology · 2025Article
- Review
- When the MET receptor kicks in to resist targeted therapies.Oncogene · 2021Review
- Aberrant activation of hepatocyte growth factor/MET signaling promotes β-catenin-mediated prostatic tumorigenesis.The Journal of biological chemistry · 2020Article
- MET in human cancer: germline and somatic mutations.Annals of translational medicine · 2017Review
- cMET in NSCLC: Can We Cut off the Head of the Hydra? From the Pathway to the Resistance.Cancers · 2015Review
- Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma.Neoplasia (New York, N.Y.) · 2005Article
- Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- The Ron oncogenic activity induced by the MEN2B-like substitution overcomes the requirement for the multifunctional docking site.Oncogene · 2000Article
- Article
- Two mutations affecting conserved residues in the Met receptor operate via different mechanisms.Oncogene · 2000Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in Met have been identified in human cancer, and we have previously shown that these mutations deregulate the enzymatic activity of this tyrosine kinase receptor, thereby unleashing its oncogenic potential. Signal transduction via wild type Met has been shown to require the autophosphorylation of two tyrosine doublets; Y8,9 which functions to enhance enzymatic activity, and Y14,15 which provides docking sites for signaling molecules, and in the present investigation we examine the importance of these residues for signaling via mutationally activated Met. We find that activating mutations introduced into a membrane-spanning Met receptor circumvent the normally stringent requirement for Y8,9 phosphorylation, and do so in a largely ligand-dependent fashion. Similarly, activating mutations introduced into a constitutively dimerized cytoplasmic form of Met (i.e. Tpr-Met) facilitate its autophosphorylation and oncogenic activity in the absence of Y8,9 phosphorylation. We also find that activating mutations allow a membrane-spanning Met receptor to overcome the requirement for the Y14,15 phosphorylation in a manner which is largely ligand-independent. These findings support a model whereby activating mutations stabilize an active conformation of the Met kinase via a mechanism which can function independently of Y8,9 autophosphorylation and suggest that signaling via wild type Met and mutationally activated Met may proceed through distinct pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.