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Vol. 9, Issue 7, 1863-1871, July 1998

and
Departments of
*Vascular Biology,
Adhesion to ECM is required for many cell functions including
cytoskeletal organization, migration, and proliferation. We observed
that when cells first adhere to extracellular matrix, they spread
rapidly by extending filopodia-like projections and lamellipodia. These
structures are similar to the Rac- and Cdc42-dependent structures
observed in growth factor-stimulated cells. We therefore investigated
the involvement of Rac and Cdc42 in adhesion and spreading on the ECM
protein fibronectin. We found that integrin-dependent adhesion
led to the rapid activation of p21-activated kinase, a downstream
effector of Cdc42 and Rac, suggesting that integrins activate
at least one of these GTPases. Dominant negative mutants of Rac and
Cdc42 inhibit cell spreading in such a way as to suggest that
integrins activate Cdc42, which leads to the subsequent
activation of Rac; both GTPases then contribute to cell spreading.
These results demonstrate that initial integrin-dependent
activation of Rac and Cdc42 mediates cell spreading.
Immunology, and
§Cell Biology, The Scripps Research Institute, La Jolla,
California 92037
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M. S. Roberts, A. J. Woods, T. C. Dale, P. van der Sluijs, and J. C. Norman Protein Kinase B/Akt Acts via Glycogen Synthase Kinase 3 To Regulate Recycling of {alpha}v{beta}3 and {alpha}5{beta}1 Integrins Mol. Cell. Biol., February 15, 2004; 24(4): 1505 - 1515. [Abstract] [Full Text] [PDF] |
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P. D. Arora, M. Glogauer, A. Kapus, D. J. Kwiatkowski, and C. A. McCulloch Gelsolin Mediates Collagen Phagocytosis through a Rac-dependent Step Mol. Biol. Cell, February 1, 2004; 15(2): 588 - 599. [Abstract] [Full Text] [PDF] |
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G. Schlunck, H. Damke, W. B. Kiosses, N. Rusk, M. H. Symons, C. M. Waterman-Storer, S. L. Schmid, and M. A. Schwartz Modulation of Rac Localization and Function by Dynamin Mol. Biol. Cell, January 1, 2004; 15(1): 256 - 267. [Abstract] [Full Text] [PDF] |
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E. Tufvesson and G. Westergren-Thorsson Biglycan and decorin induce morphological and cytoskeletal changes involving signalling by the small GTPases RhoA and Rac1 resulting in lung fibroblast migration J. Cell Sci., December 1, 2003; 116(23): 4857 - 4864. [Abstract] [Full Text] [PDF] |
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L. S. Price, M. Langeslag, J. P. t. Klooster, P. L. Hordijk, K. Jalink, and J. G. Collard Calcium Signaling Regulates Translocation and Activation of Rac J. Biol. Chem., October 10, 2003; 278(41): 39413 - 39421. [Abstract] [Full Text] [PDF] |
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I. Carton, D. Hermans, and J. Eggermont Hypotonicity induces membrane protrusions and actin remodeling via activation of small GTPases Rac and Cdc42 in Rat-1 fibroblasts Am J Physiol Cell Physiol, October 1, 2003; 285(4): C935 - C944. [Abstract] [Full Text] [PDF] |
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K. Bialkowska, Y. Zaffran, S. C. Meyer, and J. E. B. Fox 14-3-3{zeta} Mediates Integrin-induced Activation of Cdc42 and Rac: PLATELET GLYCOPROTEIN Ib-IX REGULATES INTEGRIN-INDUCED SIGNALING BY SEQUESTERING 14-3-3{zeta} J. Biol. Chem., August 29, 2003; 278(35): 33342 - 33350. [Abstract] [Full Text] [PDF] |
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P. Hou, L. Estrada, A. W. Kinley, J. T. Parsons, A. B. Vojtek, and J. L. Gorski Fgd1, the Cdc42 GEF responsible for Faciogenital Dysplasia, directly interacts with cortactin and mAbp1 to modulate cell shape Hum. Mol. Genet., August 15, 2003; 12(16): 1981 - 1993. [Abstract] [Full Text] [PDF] |
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E. Tzima, W. B. Kiosses, M. A. del Pozo, and M. A. Schwartz Localized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress J. Biol. Chem., August 15, 2003; 278(33): 31020 - 31023. [Abstract] [Full Text] [PDF] |
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L. J. Sundberg, L. M. Galante, H. M. Bill, C. P. Mack, and J. M. Taylor An Endogenous Inhibitor of Focal Adhesion Kinase Blocks Rac1/JNK but Not Ras/ERK-dependent Signaling in Vascular Smooth Muscle Cells J. Biol. Chem., August 8, 2003; 278(32): 29783 - 29791. [Abstract] [Full Text] [PDF] |
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K. A. DeMali and K. Burridge Coupling membrane protrusion and cell adhesion J. Cell Sci., June 15, 2003; 116(12): 2389 - 2397. [Abstract] [Full Text] [PDF] |
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A. Holub, J. Byrnes, S. Anderson, L. Dzaidzio, N. Hogg, and A. Huttenlocher Ligand density modulates eosinophil signaling and migration J. Leukoc. Biol., May 1, 2003; 73(5): 657 - 664. [Abstract] [Full Text] [PDF] |
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L. A. Puto, K. Pestonjamasp, C. C. King, and G. M. Bokoch p21-activated Kinase 1 (PAK1) Interacts with the Grb2 Adapter Protein to Couple to Growth Factor Signaling J. Biol. Chem., March 7, 2003; 278(11): 9388 - 9393. [Abstract] [Full Text] [PDF] |
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C. K. Thodeti, R. Albrechtsen, M. Grauslund, M. Asmar, C. Larsson, Y. Takada, A. M. Mercurio, J. R. Couchman, and U. M. Wewer ADAM12/Syndecan-4 Signaling Promotes beta 1 Integrin-dependent Cell Spreading through Protein Kinase Calpha and RhoA J. Biol. Chem., March 7, 2003; 278(11): 9576 - 9584. [Abstract] [Full Text] [PDF] |
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F. Grinnell, C.-H. Ho, E. Tamariz, D. J. Lee, and G. Skuta Dendritic Fibroblasts in Three-dimensional Collagen Matrices Mol. Biol. Cell, February 1, 2003; 14(2): 384 - 395. [Abstract] [Full Text] [PDF] |
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