Role of the PI3K Regulatory Subunit in the Control of Actin Organization and Cell Migration

doi:10.1083/jcb.151.2.249

Get More Out of Microscopy - Agilent iMIC 2000

Published online 18 October 2000. doi:10.1083/jcb.151.2.249

This Article

	Full Text
	PDF (Full Text)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Jiménez, C.
	Articles by Carrera, A. C.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Jiménez, C.
	Articles by Carrera, A. C.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2000/10/249/ $5.00
The Journal of Cell Biology, Volume 151, Number 2, October 16, 2000 249-262

Original Article

Role of the PI3K Regulatory Subunit in the Control of Actin Organization and Cell Migration

Concepción Jiménez^a, Rosario Armas Portela^b, Mario Mellado^a, Jose Miguel Rodríguez-Frade^a, John Collard^c, Antonio Serrano^a, Carlos Martínez-A^a, Jesus Avila^b, and Ana C. Carrera^a
^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

Correspondence to: Ana C. Carrera, Department of Immunology and Oncology, Centro Nacional de Biotecnología, Carretera de Colmenar Km 16, Cantoblanco, Madrid E-28049, Spain. Tel:34-91-585-4849 Fax:34-91-372-0493

Cell migration represents an important cellular response thatutilizes cytoskeletal reorganization as its driving force. Here,we describe a new signaling cascade linking PDGF receptor stimulationto actin rearrangements and cell migration. We demonstrate thatPDGF activates Cdc42 and its downstream effector N-WASP to mediatefilopodia formation, actin stress fiber disassembly, and a reductionin focal adhesion complexes. Induction of the Cdc42 pathwayis independent of phosphoinositide 3-kinase (PI3K) enzymaticactivity, but it is dependent on the p85 ${alpha}$ regulatory subunitof PI3K. Finally, data are provided showing that activationof this pathway is required for PDGF-induced cell migrationon collagen. These observations show the essential role of thePI3K regulatory subunit p85 ${alpha}$ in controlling PDGF receptor–inducedcytoskeletal changes and cell migration, illustrating a novelsignaling pathway that links receptor stimulation at the cellmembrane with actin dynamics.

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

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Senft, J., Helfer, B., Frisch, S. M. (2007). Caspase-8 Interacts with the p85 Subunit of Phosphatidylinositol 3-Kinase to Regulate Cell Adhesion and Motility. Cancer Res. 67: 11505-11509 [Abstract] [Full Text]
Komatsu, S., Ikebe, M. (2007). The Phosphorylation of Myosin II at the Ser1 and Ser2 Is Critical for Normal Platelet-derived Growth Factor induced Reorganization of Myosin Filaments. Mol. Biol. Cell 18: 5081-5090 [Abstract] [Full Text]
Alcazar, I., Marques, M., Kumar, A., Hirsch, E., Wymann, M., Carrera, A. C., Barber, D. F. (2007). Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation. J. Exp. Med. 204: 2977-2987 [Abstract] [Full Text]
Frantz, C., Karydis, A., Nalbant, P., Hahn, K. M., Barber, D. L. (2007). Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179: 403-410 [Abstract] [Full Text]
Lee, Y. H., Kayyali, U. S., Sousa, A. M., Rajan, T., Lechleider, R. J., Day, R. M. (2007). Transforming Growth Factor-beta1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src. Am. J. Respir. Cell Mol. Bio. 37: 485-493 [Abstract] [Full Text]
Matheu, M. P., Deane, J. A., Parker, I., Fruman, D. A., Cahalan, M. D. (2007). Class IA Phosphoinositide 3-Kinase Modulates Basal Lymphocyte Motility in the Lymph Node. J. Immunol. 179: 2261-2269 [Abstract] [Full Text]
Raynaud, F. I., Eccles, S., Clarke, P. A., Hayes, A., Nutley, B., Alix, S., Henley, A., Di-Stefano, F., Ahmad, Z., Guillard, S., Bjerke, L. M., Kelland, L., Valenti, M., Patterson, L., Gowan, S., de Haven Brandon, A., Hayakawa, M., Kaizawa, H., Koizumi, T., Ohishi, T., Patel, S., Saghir, N., Parker, P., Waterfield, M., Workman, P. (2007). Pharmacologic Characterization of a Potent Inhibitor of Class I Phosphatidylinositide 3-Kinases. Cancer Res. 67: 5840-5850 [Abstract] [Full Text]
Taniguchi, C. M., Aleman, J. O., Ueki, K., Luo, J., Asano, T., Kaneto, H., Stephanopoulos, G., Cantley, L. C., Kahn, C. R. (2007). The p85{alpha} Regulatory Subunit of Phosphoinositide 3-Kinase Potentiates c-Jun N-Terminal Kinase-Mediated Insulin Resistance. Mol. Cell. Biol. 27: 2830-2840 [Abstract] [Full Text]
Barber, D. F., Alvarado-Kristensson, M., Gonzalez-Garcia, A., Pulido, R., Carrera, A. C. (2006). PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase. Sci Signal 2006: pe49-pe49 [Abstract] [Full Text]
Somesh, B. P., Vlahou, G., Iijima, M., Insall, R. H., Devreotes, P., Rivero, F. (2006). RacG Regulates Morphology, Phagocytosis, and Chemotaxis. Eukaryot Cell 5: 1648-1663 [Abstract] [Full Text]
Pankow, S., Bamberger, C., Klippel, A., Werner, S. (2006). Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase. J. Cell Sci. 119: 4033-4046 [Abstract] [Full Text]
Lee, J. G., Kay, E. P. (2006). Cross-talk among Rho GTPases Acting Downstream of PI 3-Kinase Induces Mesenchymal Transformation of Corneal Endothelial Cells Mediated by FGF-2.. IOVS 47: 2358-2368 [Abstract] [Full Text]
Lee, J. G., Kay, E. P. (2006). FGF-2-Induced Wound Healing in Corneal Endothelial Cells Requires Cdc42 Activation and Rho Inactivation through the Phosphatidylinositol 3-Kinase Pathway.. IOVS 47: 1376-1386 [Abstract] [Full Text]
Shah, K., Vincent, F. (2005). Divergent Roles of c-Src in Controlling Platelet-derived Growth Factor-dependent Signaling in Fibroblasts. Mol. Biol. Cell 16: 5418-5432 [Abstract] [Full Text]
Shimamura, T., Yasuda, J., Ino, Y., Gotoh, M., Tsuchiya, A., Nakajima, A., Sakamoto, M., Kanai, Y., Hirohashi, S. (2004). Dysadherin Expression Facilitates Cell Motility and Metastatic Potential of Human Pancreatic Cancer Cells. Cancer Res. 64: 6989-6995 [Abstract] [Full Text]
Platek, A., Mettlen, M., Camby, I., Kiss, R., Amyere, M., Courtoy, P. J. (2004). v-Src accelerates spontaneous motility via phosphoinositide 3-kinase, phospholipase C and phospholipase D, but abrogates chemotaxis in Rat-1 and MDCK cells. J. Cell Sci. 117: 4849-4861 [Abstract] [Full Text]
Lee, H. T., Lee, J. G., Na, M., Kay, E. P. (2004). FGF-2 Induced by Interleukin-1{beta} through the Action of Phosphatidylinositol 3-Kinase Mediates Endothelial Mesenchymal Transformation in Corneal Endothelial Cells. J. Biol. Chem. 279: 32325-32332 [Abstract] [Full Text]
Chung, C.-H., Wu, W.-B., Huang, T.-F. (2004). Aggretin, a snake venom-derived endothelial integrin {alpha}2{beta}1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood 103: 2105-2113 [Abstract] [Full Text]
Martinez-Gac, L., Marques, M., Garcia, Z., Campanero, M. R., Carrera, A. C. (2004). Control of Cyclin G2 mRNA Expression by Forkhead Transcription Factors: Novel Mechanism for Cell Cycle Control by Phosphoinositide 3-Kinase and Forkhead. Mol. Cell. Biol. 24: 2181-2189 [Abstract] [Full Text]
Honing, H., van den Berg, T. K., van der Pol, S. M. A., Dijkstra, C. D., van der Kammen, R. A., Collard, J. G., de Vries, H. E. (2004). RhoA activation promotes transendothelial migration of monocytes via ROCK. J. Leukoc. Biol. 75: 523-528 [Abstract] [Full Text]
Qian, Y., Corum, L., Meng, Q., Blenis, J., Zheng, J. Z., Shi, X., Flynn, D. C., Jiang, B.-H. (2004). PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration. Am. J. Physiol. Cell Physiol. 286: C153-C163 [Abstract] [Full Text]
Russell, T. D., Yan, Q., Fan, G., Khalifah, A. P., Bishop, D. K., Brody, S. L., Walter, M. J. (2003). IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor {beta}1. J. Immunol. 171: 6866-6874 [Abstract] [Full Text]
Cascone, I., Audero, E., Giraudo, E., Napione, L., Maniero, F., Philips, M. R., Collard, J. G., Serini, G., Bussolino, F. (2003). Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1. Blood 102: 2482-2490 [Abstract] [Full Text]
Alvarez, B., Garrido, E., Garcia-Sanz, J. A., Carrera, A. C. (2003). Phosphoinositide 3-Kinase Activation Regulates Cell Division Time by Coordinated Control of Cell Mass and Cell Cycle Progression Rate. J. Biol. Chem. 278: 26466-26473 [Abstract] [Full Text]
Anton, I. M., Saville, S. P., Byrne, M. J., Curcio, C., Ramesh, N., Hartwig, J. H., Geha, R. S. (2003). WIP participates in actin reorganization and ruffle formation induced by PDGF. J. Cell Sci. 116: 2443-2451 [Abstract] [Full Text]
Tan, B. L., Yazicioglu, M. N., Ingram, D., McCarthy, J., Borneo, J., Williams, D. A., Kapur, R. (2003). Genetic evidence for convergence of c-Kit- and {alpha}4 integrin-mediated signals on class IA PI-3kinase and the Rac pathway in regulating integrin-directed migration in mast cells. Blood 101: 4725-4732 [Abstract] [Full Text]
Liao, X., Thrasher, J. B., Pelling, J., Holzbeierlein, J., Sang, Q.-X. A., Li, B. (2003). Androgen Stimulates Matrix Metalloproteinase-2 Expression in Human Prostate Cancer. Endocrinology 144: 1656-1663 [Abstract] [Full Text]
Papakonstanti, E. A., Kampa, M., Castanas, E., Stournaras, C. (2003). A Rapid, Nongenomic, Signaling Pathway Regulates the Actin Reorganization Induced by Activation of Membrane Testosterone Receptors. Mol. Endocrinol. 17: 870-881 [Abstract] [Full Text]
Marino, S., Krimpenfort, P., Leung, C., van der Korput, H. A. G. M., Trapman, J., Camenisch, I., Berns, A., Brandner, S. (2003). PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development 129: 3513-3522 [Abstract] [Full Text]
Uzumcu, M., Westfall, S. D., Dirks, K. A., Skinner, M. K. (2002). Embryonic Testis Cord Formation and Mesonephric Cell Migration Requires the Phosphotidylinositol 3-Kinase Signaling Pathway. Biol. Reprod. 67: 1927-1935 [Abstract] [Full Text]
Choe, E. Y., Schoenberger, E. S., Groopman, J. E., Park, I.-W. (2002). HIV Nef Inhibits T Cell Migration. J. Biol. Chem. 277: 46079-46084 [Abstract] [Full Text]
Grill, B., Schrader, J. W. (2002). Activation of Rac-1, Rac-2, and Cdc42 by hemopoietic growth factors or cross-linking of the B-lymphocyte receptor for antigen. Blood 100: 3183-3192 [Abstract] [Full Text]
Carabeo, R. A., Grieshaber, S. S., Fischer, E., Hackstadt, T. (2002). Chlamydia trachomatis Induces Remodeling of the Actin Cytoskeleton during Attachment and Entry into HeLa Cells. Infect. Immun. 70: 3793-3803 [Abstract] [Full Text]
Sturge, J., Hamelin, J., Jones, G. E. (2002). N-WASP activation by a {beta}1-integrin-dependent mechanism supports PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator. J. Cell Sci. 115: 699-711 [Abstract] [Full Text]
Zeng, H., Zhao, D., Mukhopadhyay, D. (2002). Flt-1-mediated Down-regulation of Endothelial Cell Proliferation through Pertussis Toxin-sensitive G Proteins, beta gamma Subunits, Small GTPase CDC42, and Partly by Rac-1. J. Biol. Chem. 277: 4003-4009 [Abstract] [Full Text]
Vetterkind, S., Miki, H., Takenawa, T., Klawitz, I., Scheidtmann, K.-H., Preuss, U. (2002). The Rat Homologue of Wiskott-Aldrich Syndrome Protein (WASP)-interacting Protein (WIP) Associates with Actin Filaments, Recruits N-WASP from the Nucleus, and Mediates Mobilization of Actin from Stress Fibers in Favor of Filopodia Formation. J. Biol. Chem. 277: 87-95 [Abstract] [Full Text]
Berrou, E., Bryckaert, M. (2001). Platelet-derived Growth Factor Inhibits Smooth Muscle Cell Adhesion to Fibronectin by ERK-dependent and ERK-independent Pathways. J. Biol. Chem. 276: 39303-39309 [Abstract] [Full Text]
Robledo, M. M., Bartolome, R. A., Longo, N., Rodriguez-Frade, J. M., Mellado, M., Longo, I., van Muijen, G. N. P., Sanchez-Mateos, P., Teixido, J. (2001). Expression of Functional Chemokine Receptors CXCR3 and CXCR4 on Human Melanoma Cells. J. Biol. Chem. 276: 45098-45105 [Abstract] [Full Text]
Kang, H., Schneider, H., Rudd, C. E. (2002). Phosphatidylinositol 3-Kinase p85 Adaptor Function in T-cells. CO-STIMULATION AND REGULATION OF CYTOKINE TRANSCRIPTION INDEPENDENT OF ASSOCIATED p110. J. Biol. Chem. 277: 912-921 [Abstract] [Full Text]