Role of the PI3K regulatory subunit in the control of actin organization and cell migration

Cell migration represents an important cellular response that utilizes cyto skeletal reorganization as its driving force. Here, we describe a new signa ling cascade linking PDGF receptor stimulation to actin rearrangements and cell migration. We demonstrate that PDGF activates Cdc42 and its downstream effector N-WASP to mediate filopodia formation, actin stress fiber disasse mbly, and a reduction in focal adhesion complexes. Induction of the Cdc42 p athway is independent of phosphoinositide 3-kinase (PI3K) enzymatic activit y, but it is dependent on the p85 alpha regulatory subunit of PI3K. Finally , data are provided showing that activation of this pathway is required for PDGF-induced cell migration on collagen. These observations show the essen tial role of the PI3K regulatory subunit p85 alpha in controlling PDGF rece ptor-induced cytoskeletal changes and cell migration, illustrating a novel signaling pathway that links receptor stimulation at the cell membrane with actin dynamics.