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Published online 16 October 2000. doi:10.1083/jcb.151.2.249
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© The Rockefeller University Press, 0021-9525/2000//249 $5.00
The Journal of Cell Biology, Volume 151, Number 2, , 2000 249-262

Original Article

Role of the Pi3k Regulatory Subunit in the Control of Actin Organization and Cell Migration



Concepción Jiméneza, Rosario Armas Portelab, Mario Melladoa, Jose Miguel Rodríguez-Fradea, John Collardc, Antonio Serranoa, Carlos Martínez-Aa, Jesus Avilab, and Ana C. Carreraa

a Department of Immunology and Oncology, Centro Nacional de Biotecnología,
b Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain
c The Netherlands Cancer Institute, Division of Cell Biology, 1066 CX, Amsterdam, The Netherlands
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Carretera de Colmenar Km 16, Cantoblanco, Madrid E-28049, Spain.34-91-372-049334-91-585-4849

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{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 essential role of the PI3K regulatory subunit p85{alpha} 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.

Key Words: N-WASP • Cdc42 • PDGF • phosphatidylinositol 3-kinase • actin cytoskeleton

© 2000 The Rockefeller University Press

Abbreviations used in this paper: Ab, antibody; DN, dominant negative; ECM, extracellular matrix; F-actin, filamentous actin; GEF, guanine nucleotide exchange factors; N-WASP, N-Wiskott-Aldrich Syndrome family protein; LPA, lysophosphatidic acid; PDGF, platelet-derived growth factor; PDGF-R, PDGF receptor; PI3K, phosphoinositide 3-kinase.


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