| First Author | Jenna S | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 8 | Pages | 6366-73 |
| PubMed ID | 11744688 | Mgi Jnum | J:74670 |
| Mgi Id | MGI:2158954 | Doi | 10.1074/jbc.M105516200 |
| Citation | Jenna S, et al. (2002) The Activity of the GTPase-activating Protein CdGAP Is Regulated by the Endocytic Protein Intersectin. J Biol Chem 277(8):6366-73 |
| abstractText | The Rho GTPases RhoA, Rac1, and Cdc42 play a major role in regulating the reorganization of the actin cytoskeleton. We recently identified CdGAP, a novel GTPase-activating protein with activity toward Rac1 and Cdc42. CdGAP consists of a N-terminal GAP domain, a central domain, and a C-terminal proline-rich domain. Here we show that through a subset of its Src homology 3 domains, the endocytic protein intersectin interacts with CdGAP. In platelet-derived growth factor-stimulated Swiss 3T3 cells, intersectin co-localizes with CdGAP and inhibits its GAP activity toward Rac1. Intersectin-Src homology 3 also inhibits CdGAP activity in GAP assays in vitro. Although the C-terminal proline-rich domain of CdGAP is required for the regulation of its GAP activity by intersectin both in vivo and in vitro, it is not necessary for CdGAP-intersectin interaction. Our data suggest that the central domain of CdGAP is required for CdGAP-intersectin interaction. Thus, we propose a model in which intersectin binding results in a change of CdGAP conformation involving the proline-rich domain that leads to the inhibition of its GAP activity. These observations provide the first demonstration of a direct regulation of RhoGAP activity through a protein-protein interaction and suggest a function for intersectin in Rac1 regulation and actin dynamics. |
