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| Content Provider | PubMed Central |
|---|---|
| Author | Wang, Hongbin Yang, Chengfeng Coluccio, Leskow Federico Sun, Jing Canagarajah, Bertram Hurley, James H. Kazanietz, Marcelo G. |
| Copyright Year | 2006 |
| Abstract | Although receptor-mediated regulation of small G-proteins and the cytoskeleton is intensively studied, the mechanisms for attenuation of these signals are poorly understood. In this study, we have identified the Rac-GAP β2-chimaerin as an effector of the epidermal growth factor receptor (EGFR) via coupling to phospholipase Cγ (PLCγ) and generation of the lipid second messenger diacylglycerol (DAG). EGF redistributes β2-chimaerin to promote its association with the small GTPase Rac1 at the plasma membrane, as determined by FRET. This relocalization and association with Rac1 were impaired by disruption of the β2-chimaerin C1 domain as well as by PLCγ1 RNAi, thus defining β2-chimaerin as a novel DAG effector. On the other hand, GAP-deficient β2-chimaerin mutants show enhanced translocation and sustained Rac1 association in the FRET assays. Remarkably, RNAi depletion of β2-chimaerin significantly extended the duration of Rac activation by EGF, suggesting that β2-chimaerin serves as a mechanism that self-limits Rac activity in response to EGFR activation. Our results represent the first direct evidence of divergence in DAG signaling downstream of a tyrosine-kinase receptor via a PKC-independent mechanism. |
| Related Links | http://dx.doi.org/10.1038/sj.emboj.7601098 |
| Ending Page | 2074 |
| Page Count | 13 |
| Starting Page | 2062 |
| File Format | |
| ISSN | 02614189 |
| e-ISSN | 14602075 |
| Journal | The EMBO Journal |
| Issue Number | 10 |
| Volume Number | 25 |
| Language | English |
| Publisher Date | 2006-05-17 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Molecular Biology |
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