| First Author | Lee HS | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 8 | Pages | 1401-13 |
| PubMed ID | 25666508 | Mgi Jnum | J:224425 |
| Mgi Id | MGI:5662192 | Doi | 10.1128/MCB.00112-15 |
| Citation | Lee HS, et al. (2015) Protein tyrosine phosphatase-PEST and beta8 integrin regulate spatiotemporal patterns of RhoGDI1 activation in migrating cells. Mol Cell Biol 35(8):1401-13 |
| abstractText | Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor beta8 integrin that plays essential roles in directional cell motility. beta8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells. |
