The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses
Open accessAbstract
Gab1 is a substrate of the receptor tyrosine kinase c-Met and involved in c-Met–specific branching morphogenesis. It associates directly with c-Met via the c-Met–binding domain, which is not related to known phosphotyrosine-binding domains. In addition, Gab1 is engaged in a constitutive complex with the adaptor protein Grb2. We have now mapped the c-Met and Grb2 interaction sites using reverse yeast two-hybrid technology. The c-Met–binding site is localized to a 13–amino acid region unique to Gab1. Insertion of this site into the Gab1-related protein p97/Gab2 was sufficient to confer c-Met–binding activity. Association with Grb2 was mapped to two sites: a classical SH3-binding site (PXXP) and a novel Grb2 SH3 consensus-binding motif (PX(V/I)(D/N)RXXKP). To detect phosphorylation-dependent interactions of Gab1 with downstream substrates, we developed a modified yeast two-hybrid assay and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab1. In a trk-met-Gab1–specific branching morphogenesis assay, association of Gab1 with Shp2, but not PI(3)K, CRKL, or Shc was essential to induce a biological response in MDCK cells. Overexpression of a Gab1 mutant deficient in Shp2 interaction could also block HGF/SF-induced activation of the MAPK pathway, suggesting that Shp2 is critical for c-Met/Gab1-specific signaling.
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Metadata
- Authors
- Schaeper, U., Gehring, N. H., Fuchs, K. P., Sachs, M., Kempkes, B., & Birchmeier, W.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2000-06-26
- Volume
- 149
- Issue
- 7
- Pages
- 1419-1432
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2137934927
- Cited by
- 346
- References
- 93
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Schaeper, U., Gehring, N. H., Fuchs, K. P., Sachs, M., Kempkes, B., & Birchmeier, W. (2000). Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses. The Journal of Cell Biology. https://doi.org/10.1083/jcb.149.7.1419
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