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Plexin-B1 functions as an R-Ras GTPase-activating protein (GAP) and directly and specifically down regulates R-Ras activity in response to Sema4D, inducing growth cone collapse. R-Ras inactivation promotes PI3K and Akt inactivation followed by GSK-3beta activation and CRMP inactivation. R-Ras inactivation also inhibits cell migration by regulating beta1 integrin activity.