Figure 7.
PI3K and PKC contribute to R-Ras induced cell migration. (a) Pretreatment with PI3K inhibitors Wortmannin (Wtm, 30 nM) or LY294002 (LY, 25 μM) partially inhibits the migration of cells expressing activated R-Ras(87L) or (38V), or TC21(72L) across collagen. *P < 0.05 compared with DMSO-treated samples for each cell line shown. (b) Pretreatment of cells with the PI3K inhibitor, Wortmannin (Wtm, 30 nM), or the PKC inhibitor, bisindolylmalemide (Bis, 1 μM), or both. Wortmannin and bisindolylmalemide alone each partially inhibits R-Ras– induced migration of cells across collagen. Together, Wortmannin and bisindolylmalemide have an additive effect and completely inhibit R-Ras–induced migration. *P < 0.05 compared with DMSO-treated samples for each cell line. (c) Pretreatment of cells with the MEK inhibitor, PD98059 (PD98, 25 μM) has no effect on the migration across collagen of cells expressing activated R-Ras(87L) or (38V) or TC21(72L). In contrast, PD98059 completely inhibits migration induced by activated K-Ras(12V). *P < 0.05 compared with DMSO-treated samples for each cell line.