ArticleOncogene2002
Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 65 citations in OpenAlex.
- Autoregulation of the MET receptor tyrosine kinase by its intracellular juxtamembrane domain.The Biochemical journal · 2025Article
- PI3K-dependent GAB1/Erk phosphorylation renders head and neck squamous cell carcinoma sensitive to PI3Kα inhibitors.Cell death & disease · 2025Article
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
- The Role of GAB1 in Cancer.Cancers · 2023Review
- p52Shc regulates the sustainability of ERK activation in a RAF-independent manner.Molecular biology of the cell · 2021Article
- Biphasic spatiotemporal regulation of GRB2 dynamics by p52SHC for transient RAS activation.Biophysics and physicobiology · 2021Article
- Identification of functionally connected multi-omic biomarkers for Alzheimer's disease using modularity-constrained Lasso.PloS one · 2020Article
- Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins.Aging · 2019Article
- Insights into the Shc Family of Adaptor Proteins.Journal of molecular signaling · 2017Article
- Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor.The Biochemical journal · 2016Article
- Biology of MET: a double life between normal tissue repair and tumor progression.Annals of translational medicine · 2015Review
- Article
- Met receptor tyrosine kinase signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia.Journal of cell science · 2012Article
- Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET.The Journal of biological chemistry · 2011Article
- Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance.Journal of cancer research and clinical oncology · 2009Article
- The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains.Molecular neurodegeneration · 2009Article
- Identification of Shc Src homology 2 domain-binding peptoid-peptide hybrids.Journal of medicinal chemistry · 2009Article
- KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic relevance.Oncogene · 2007Article
- From Tpr-Met to Met, tumorigenesis and tubes.Oncogene · 2007Review
- Gab1 is required for cell cycle transition, cell proliferation, and transformation induced by an oncogenic met receptor.Molecular biology of the cell · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many human cancers have been associated with the deregulation of receptor tyrosine kinases (RTK). However, the individual contribution of receptor-associated signaling proteins in cellular transformation and metastasis is poorly understood. To examine the role of RTK activated signal transduction pathways to processes involved in cell transformation, we have exploited the oncogenic derivative of the Met RTK (Tpr-Met). Unlike other RTKs, twin tyrosine residues in the carboxy-terminal tail of the Met oncoprotein and receptor are required for all biological and transforming activities, and a mutant lacking these tyrosines is catalytically active but non transforming. Using this mutant we have inserted oligonucleotide cassettes, each encoding a binding site for a specific signaling protein derived from other RTKs. We have generated variant forms of the Tpr-Met oncoprotein with the ability to bind individually to the p85 subunit of PI3'K, PLCgamma, or to the Grb2 or Shc adaptor proteins. Variants that recruit the Shc or Grb2 adaptor proteins generated foci of morphologically transformed fibroblast cells and induced anchorage-independent growth, scattering of epithelial cells and experimental metastasis. In contrast, variants that bind and activate PI3'K or PLCgamma failed to generate readily detectable foci. Although cell lines expressing the PI3'K variant grew in soft-agar, these cells were non metastatic. Using this unique RTK oncoprotein model, we have established that Grb2 or Shc dependent signaling pathways are sufficient for cell transformation and metastatic spread.
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Registered trials
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.