| First Author | Continolo S | Year | 2005 |
| Journal | Exp Cell Res | Volume | 302 |
| Issue | 2 | Pages | 253-69 |
| PubMed ID | 15561106 | Mgi Jnum | J:94595 |
| Mgi Id | MGI:3513574 | Doi | 10.1016/j.yexcr.2004.09.005 |
| Citation | Continolo S, et al. (2005) The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization. Exp Cell Res 302(2):253-69 |
| abstractText | Fgr participates in integrin signaling in myeloid leukocytes. To examine the role of its specific domains in regulating cell migration, we expressed various Fgr molecules in COS-7 cells. Full-length, membrane-bound Fgr, but not an N-terminal truncation mutant that distributed to an intracellular compartment, increased cell migration on fibronectin and enhanced phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PI3K), cortactin and focal adhesion kinase (FAK) at Y397 and Y576. Fgr increased Rac GTP loading, and phosphorylation of the Rac GEF Vav2, and bound to a protein complex formed by the Rho inhibitor p190RhoGAP and FAK, increasing p190RhoGAP phosphorylation, in a manner absolutely dependent on membrane localization. A kinase-defective truncation mutant of Fgr increased cell migration, albeit to a much lower extent than full-length Fgr, and was found to associate with the plasma membrane, to activate Rac and to form complexes with p190RhoGAP/FAK. Formation of complexes between p190RhoGAP, Fgr, and the FAK-related protein Pyk2 were also detected in murine macrophages. These findings suggest that the proto-oncogene Fgr regulates cell migration impinging on a signaling pathway implicating FAK/Pyk2 and leading to activation of Rac and the Rho inhibitor p190RhoGAP. |
