Role of the PI3K regulatory subunit in the control of actin organization and cell migration.
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 p85alpha 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 p85alpha 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.
Jiménez
C
C
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain.
Portela
R A
RA
Mellado
M
M
Rodríguez-Frade
J M
JM
Collard
J
J
Serrano
A
A
Martínez-A
C
C
Avila
J
J
Carrera
A C
AC
D016475:3T3 Cells; D008841:Actin Cytoskeleton; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D051379:Mice; D018715:Microscopy, Video; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021122:Protein Subunits; D011554:Pseudopodia; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D019869:Phosphatidylinositol 3-Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D020764:cdc42 GTP-Binding Protein