Copyright © by The Rockefeller University Press
Cell migration represents an important cellular response that utilizes cytoskeletal reorganization as its driving force. Here, we describe a new signaling 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 disassembly, and a reduction in focal adhesion complexes. Induction of the Cdc42 pathway is independent of phosphoinositide 3-kinase (PI3K) enzymatic activity,
but it is dependent on the p85 a
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 essential
role of the PI3K regulatory subunit p85
a in controlling PDGF receptor–induced cytoskeletal changes and cell migration, illustrating a novel signaling pathway
that links receptor stimulation at the cell membrane with actin dynamics
Peer reviewed