ArticleMolecular and cellular biology2001
The multisubstrate adapter Gab1 regulates hepatocyte growth factor (scatter factor)-c-Met signaling for cell survival and DNA repair.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 76 citations in OpenAlex.
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Thiosemicarbazones suppress expression of the c-Met oncogene by mechanisms involving lysosomal degradation and intracellular shedding.The Journal of biological chemistry · 2020Article
- IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer.Frontiers in pharmacology · 2020Article
- Enhancing the Radiation Response in KRAS Mutant Colorectal Cancers Using the c-Met Inhibitor Crizotinib.Translational oncology · 2019Article
- Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS.Scientific reports · 2018Article
- The Role of PI3K in Met Driven Cancer: A Recap.Frontiers in molecular biosciences · 2018Review
- Molecular and genetic properties of tumors associated with local immune cytolytic activity.Cell · 2015Article
- c-Met and Other Cell Surface Molecules: Interaction, Activation and Functional Consequences.Biomedicines · 2015Review
- Monoclonal Antibodies against the MET/HGF Receptor and Its Ligand: Multitask Tools with Applications from Basic Research to Therapy.Biomedicines · 2014Review
- Crosstalk between nuclear MET and SOX9/β-catenin correlates with castration-resistant prostate cancer.Molecular endocrinology (Baltimore, Md.) · 2014Article
- The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response-Biological and Clinical Aspects.Cancers · 2013Article
- Effect of PF-02341066 and radiation on non-small cell lung cancer cells.Oncology reports · 2013Article
- MET receptor tyrosine kinase as an autism genetic risk factor.International review of neurobiology · 2013Review
- Anti-apoptotic role of caspase-cleaved GAB1 adaptor protein in hepatocyte growth factor/scatter factor-MET receptor protein signaling.The Journal of biological chemistry · 2012Article
- C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2012Article
- Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET.Cancer research · 2012Article
- miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222.Oncogene · 2012Article
- Hepatocyte growth factor in lung repair and pulmonary fibrosis.Acta pharmacologica Sinica · 2011Review
- The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells.Radiation oncology (London, England) · 2009Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte growth factor (scatter factor) (HGF/SF) is a pleiotrophic mediator of epithelial cell motility, morphogenesis, angiogenesis, and tumorigenesis. HGF/SF protects cells against DNA damage by a pathway from its receptor c-Met to phosphatidylinositol 3-kinase (PI3K) to c-Akt, resulting in enhanced DNA repair and decreased apoptosis. We now show that protection against the DNA-damaging agent adriamycin (ADR; topoisomerase IIalpha inhibitor) requires the Grb2-binding site of c-Met, and overexpression of the Grb2-associated binder Gab1 (a multisubstrate adapter required for epithelial morphogenesis) inhibits the ability of HGF/SF to protect MDCK epithelial cells against ADR. In contrast to Gab1 and its homolog Gab2, overexpression of c-Cb1, another multisubstrate adapter that associates with c-Met, did not affect protection. Gab1 blocked the ability of HGF/SF to cause the sustained activation of c-Akt and c-Akt signaling (FKHR phosphorylation). The Gab1 inhibition of sustained c-Akt activation and of cell protection did not require the Gab1 pleckstrin homology or SHP2 phosphatase-binding domain but did require the PI3K-binding domain. HGF/SF protection of parental MDCK cells was blocked by wortmannin, expression of PTEN, and dominant negative mutants of p85 (regulatory subunit of PI3K), Akt, and Pak1; the protection of cells overexpressing Gab1 was restored by wild-type or activated mutants of p85, Akt, and Pak1. These findings suggest that the adapter Gab1 may redirect c-Met signaling through PI3K away from a c-Akt/Pak1 cell survival pathway.
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