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- Title
Semaphorin 4D/Plexin-B1--mediated R-Ras GAP activity inhibits cell migration by regulating ß<sub>1</sub> integrin activity.
- Authors
Oinuma, Izumi; Katoh, Hironori; Negishi, Manabu
- Abstract
Plexins are cell surface receptors for semaphorins and regulate cell migration in many cell types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) for R-Ras, a member of Ras family GTPases implicated in regulation of integrin activity and cell migration (Oinuma, I., Y. Ishikawa, H. Katoh, and M. Negishi. 2004. Science. 305:862-865). We characterized the role of R-Ras downstream of Sema4D/Plexin-B1 in cell migration. Activation of Plexin-B1 by Sema4D suppressed the ECM-dependent R-Ras activation, R-Ras-mediated phosphatydylinositol 3-kinase activation, and β[sub 1] integrin activation through its R-Ras GAP domain, leading to inhibition of cell migration. In addition, inactivation of R-Ras by overexpression of the R-Ras-specific GAP or knockdown of R-Ras by RNA interference was sufficient for suppressing β[sub 1] integrin activation and cell migration in response to the ECM stimulation. Thus, we conclude that R-Ras activity is critical for ECM-mediated β[sub 1] integrin activation and cell migration and that inactivation of R-Ras by Sema4D/ Plexin-B1-mediated R-Ras GAP activity controls cell migration by modulating the activity of β[sub 1] integrins.
- Subjects
CELL membranes; CELL migration; CELL receptors; GUANOSINE triphosphatase; INTEGRINS
- Publication
Journal of Cell Biology, 2006, Vol 173, Issue 4, p601
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200508204