| First Author | Hetey SE | Year | 2005 |
| Journal | Exp Cell Res | Volume | 311 |
| Issue | 1 | Pages | 147-56 |
| PubMed ID | 16183059 | Mgi Jnum | J:104458 |
| Mgi Id | MGI:3612000 | Doi | 10.1016/j.yexcr.2005.08.011 |
| Citation | Hetey SE, et al. (2005) Tyrosine-phosphorylated Hic-5 inhibits epidermal growth factor-induced lamellipodia formation. Exp Cell Res 311(1):147-56 |
| abstractText | The focal adhesion protein Hic-5, a homologue to paxillin, has been shown to be tyrosine-phosphorylated in fibroblasts in response to stimuli such as osmotic stress, serum, LPA and endothelin. However, the function of this modification to Hic-5 is unclear. Herein, we show that Hic-5 is tyrosine-phosphorylated on residues 38 and 60 following epidermal growth factor (EGF) treatment of COS-7 cells, coincident with an increase in peripheral actin reorganization. To explore the role of Hic-5 phosphorylation in this process, we introduced wild-type (WT) and mutant Hic-5 constructs into COS-7 cells and determined that EGF-induced lamellipodia formation was suppressed by WT Hic-5. This effect required localization to focal adhesions as well as phosphorylation of Hic-5 as overexpression of both a non-targeting and a non-phosphorylatable Hic-5 failed to inhibit peripheral actin reorganization. Interestingly, overexpression of non-phosphorylatable Y31/118F or WT paxillin did not affect lamellipodia formation, indicating that this effect is specific to Hic-5. The EGF-induced lamellipodia were Rac-dependent and overexpressed WT Hic-5, but not non-phosphorylatable Hic-5 inhibited Rac activation. Our data suggest that Hic-5 tyrosine phosphorylation functions to regulate signaling associated with lamellipodia formation, a process fundamental to cell motility. |
