ArticleMolecular biology of the cell2003
Membrane targeting of Grb2-associated binder-1 (Gab1) scaffolding protein through Src myristoylation sequence substitutes for Gab1 pleckstrin homology domain and switches an epidermal growth factor response to an invasive morphogenic program.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- The HGF/MET Axis in Advanced Prostate Cancer: From Context-Dependent Biology to Biomarker-Driven Therapeutic Strategies.Cancers · 2026Review
- PI3K-dependent GAB1/Erk phosphorylation renders head and neck squamous cell carcinoma sensitive to PI3Kα inhibitors.Cell death & disease · 2025Article
- Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling.Cell reports · 2018Article
- Biomarker development in MET-targeted therapy.Oncotarget · 2016Review
- PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling.Cellular signalling · 2016Article
- Novel role for p21-activated kinase 2 in thrombin-induced monocyte migration.The Journal of biological chemistry · 2013Article
- Phosphoinositides differentially regulate protrudin localization through the FYVE domain.The Journal of biological chemistry · 2012Article
- An overview of the c-MET signaling pathway.Therapeutic advances in medical oncology · 2011Article
- 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
- Phosphatidylinositol-(4,5)-bisphosphate enables efficient secretion of HIV-1 Tat by infected T-cells.The EMBO journal · 2010Article
- Pak4, a novel Gab1 binding partner, modulates cell migration and invasion by the Met receptor.Molecular and cellular biology · 2009Article
- From Tpr-Met to Met, tumorigenesis and tubes.Oncogene · 2007Review
- Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy.International journal of medical sciences · 2006Article
- Evidence for the occurrence of membrane-type serine protease 1/matriptase on the basolateral sides of enterocytes.The Biochemical journal · 2005Article
- MYRbase: analysis of genome-wide glycine myristoylation enlarges the functional spectrum of eukaryotic myristoylated proteins.Genome biology · 2004Article
- KRAS and MET in non-small-cell lung cancer: two of the new kids on the 'drivers' block.Therapeutic advances in respiratory diseaseReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatocyte growth factor receptor tyrosine kinase Met promotes cell dissociation and the inherent morphogenic program of epithelial cells. In a search for substrates downstream from Met, we have previously identified the Grb2-associated binder-1 (Gab1) as critical for the morphogenic program. Gab1 is a scaffold protein that acts to diversify the signal downstream from the Met receptor through its ability to couple with multiple signal transduction pathways. Gab1 contains a pleckstrin homology (PH) domain with specificity for phosphatidylinositol 3,4,5-trisphosphate. The phospholipid binding capacity of the Gab1 PH domain is required for the localization of Gab1 at sites of cell-cell contact in colonies of epithelial cells and for epithelial morphogenesis, suggesting that PH domain-dependent subcellular localization of Gab1 is a prerequisite for function. We have investigated the requirement for membrane localization of Gab1 for biological activity. We show that substitution of the Gab1 PH domain with the myristoylation signal from the c-Src protein is sufficient to replace the Gab1 PH domain for epithelial morphogenesis. The membrane targeting of Gab1 enhances Rac activity in the absence of stimulation and switches a nonmorphogenic noninvasive response to epidermal growth factor to a morphogenic invasive program. These results suggest that the subcellular localization of Gab1 is a critical determinant for epithelial morphogenesis and invasiveness.
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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.