Linker region of Akt1/protein kinase Bα mediates platelet-derived growth factor-induced translocation and cell migration

Abstract

The phosphatidylinositol 3-kinase (PI3K) signaling pathway(s) is activated by a variety of agonists to regulate cell migration. Here, we show that the stimulation of mouse embryonic fibroblasts with platelet-derived growth factor (PDGF) induces migration in a PI3K-dependent manner. Cells lacking Akt1/PKBα exhibit impaired migration and peripheral ruffling in response to PDGF stimulation, whereas cells lacking Akt2/PKBβ are normal. In addition, over-expression of Akt1/PKBα but not Akt2/PKBβ is sufficient to restore PDGF-induced cell migration in an Akt1/PKBα and Akt2/PKBβ deficient background. In response to PDGF stimulation, Akt1/PKBα selectively translocates to membrane ruffles, however, this localization is abrogated by substituting the linker region of Akt2/PKBβ. Similarly, expression of an Akt2/PKBα chimera containing the linker region of Akt1/PKBα restored PDGF-induced migration in cells lacking both Akt1/PKBα and Akt2/PKBβ. Finally, over-expression of constitutively active Rac rescues PDGF-induced migration defects in cells lacking Akt1/PKBα. Given these results, we suggest that Akt1/PKBα controls cell migration by selectively translocating to the leading edge and activating Rac.