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Science 8 May 1998:
Vol. 280. no. 5365, pp. 898 - 902
DOI: 10.1126/science.280.5365.898
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Reports

Role of Rac1 and Oxygen Radicals in Collagenase-1 Expression Induced by Cell Shape Change

Farrah Kheradmand, Erica Werner, Patrice Tremble, * Marc Symons, Zena Werb dagger

Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to alpha 5beta 1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate-binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B-dependent transcriptional regulation of interleukin-1alpha , which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease. The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion.

F. Kheradmand, Department of Medicine, University of California, San Francisco, CA, USA.
E. Werner, P. Tremble, Z. Werb, Department of Anatomy, University of California, San Francisco, CA 94143-0750, USA.
M. Symons, Onyx Pharmaceuticals, Richmond, CA 94806, USA.
*   Present address: Baxter Healthcare Corp., Round Lake, IL 60073, USA.

dagger    To whom correspondence should be addressed. E-mail: zena{at}itsa.ucsf.edu

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A Redox Signaling Mechanism for Density-dependent Inhibition of Cell Growth.
G. Pani, R. Colavitti, B. Bedogni, R. Anzevino, S. Borrello, and T. Galeotti (2000)
J. Biol. Chem. 275, 38891-38899
   Abstract »    Full Text »    PDF »
Rac1 Mediates Type I Collagen-dependent MMP-2 Activation. ROLE IN CELL INVASION ACROSS COLLAGEN BARRIER.
Y. Zhuge and J. Xu (2001)
J. Biol. Chem. 276, 16248-16256
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Dbl and the Rho GTPases Activate NFkappa B by Ikappa B Kinase (IKK)-dependent and IKK-independent Pathways.
M. S. Cammarano and A. Minden (2001)
J. Biol. Chem. 276, 25876-25882
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Manganese Superoxide Dismutase Signals Matrix Metalloproteinase Expression via H2O2-dependent ERK1/2 Activation.
A. C. Ranganathan, K. K. Nelson, A. M. Rodriguez, K.-H. Kim, G. B. Tower, J. L. Rutter, C. E. Brinckerhoff, T.-T. Huang, C. J. Epstein, J. J. Jeffrey, et al. (2001)
J. Biol. Chem. 276, 14264-14270
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Basic Calcium Phosphate Crystals Induce Matrix Metalloproteinase-1 through the Ras/Mitogen-activated Protein Kinase/c-Fos/AP-1/Metalloproteinase 1 Pathway. INVOLVEMENT OF TRANSCRIPTION FACTOR BINDING SITES AP-1 AND PEA-3.
Y. Sun, L. Wenger, C. E. Brinckerhoff, R. R. Misra, and H. S. Cheung (2002)
J. Biol. Chem. 277, 1544-1552
   Abstract »    Full Text »    PDF »


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