![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
![[img]](http://edoc.mdc-berlin.de/style/images/fileicons/application_pdf.png) |
PDF
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
540kB |
| Item Type: | Article |
|---|---|
| Title: | Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses |
| Creators Name: | Schaeper, U. and Gehring, N.H. and Fuchs, K.P. and Sachs, M. and Kempkes, B. and Birchmeier, W. |
| Abstract: | 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. |
| Keywords: | Gab1, c-Met-Binding Site, Morphogenesis, Shp2, Reverse Yeast Two-Hybrid Analysis |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 149 |
| Number: | 7 |
| Page Range: | 1419-1432 |
| Date: | 26 June 2000 |
| Additional Information: | Copyright (c) 2000 by The Rockefeller University Press |
| Official Publication: | http://www.jcb.org/cgi/content/abstract/149/7/1419 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
