title: Role of the PI3K regulatory subunit in the control of actin organization and cell migration.
abstract: 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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jiménez
authors.forename: R A
authors.initials: RA
authors.lastname: Portela
authors.forename: M
authors.initials: M
authors.lastname: Mellado
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez-Frade
authors.forename: J
authors.initials: J
authors.lastname: Collard
authors.forename: A
authors.initials: A
authors.lastname: Serrano
authors.forename: C
authors.initials: C
authors.lastname: Martínez-A
authors.forename: J
authors.initials: J
authors.lastname: Avila
authors.forename: A C
authors.initials: AC
authors.lastname: Carrera
mesh_terms: 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
chemical_list: 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