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...

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Detalles Bibliográficos
Autores: Jiménez, Concepción, Armas Portela, Rosario, Mellado, Mario, Rodríguez-Frade, José Miguel, Collard, John, Serrano Moral, Antonio, Martínez-Alonso, Carlos, Ávila, Jesús, Carrera, Ana C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2000
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::6b54b204fe1dcce4f2cb05165f1acbf7
Acceso en línea:http://hdl.handle.net/10261/3386
Access Level:acceso abierto
Palabra clave:N-WASP
Cdc42
PDGF
Phosphatidylinositol 3-kinase
Actin cytoskeleton
Descripción
Sumario: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.