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Science 13 September 1996:
Vol. 273. no. 5281, pp. 1551 - 1555
DOI: 10.1126/science.273.5281.1551
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Reports

Regulation of Integrin Function by the Urokinase Receptor

Ying Wei, Matvey Lukashev, Daniel I. Simon, Sarah C. Bodary, Steven Rosenberg, Michael V. Doyle, Harold A. Chapman *

Integrin function is central to inflammation, immunity, and tumor progression. The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR. Interaction of soluble uPAR with the active conformer of integrins mimicked the inhibitory effects of membrane uPAR. Both uPAR-mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes. These data provide a paradigm for regulation of integrins in which a nonintegrin membrane receptor interacts with and modifies the function of activated integrins.

Y. Wei, D. I. Simon, H. A. Chapman, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
M. Lukashev, Department of Stomatology, University of California, San Francisco, CA 94143, USA.
S. C. Bodary, Genentech, South San Francisco, CA 94080, USA.
S. Rosenberg and M. V. Doyle, Chiron Corporation, Emeryville, CA 94608, USA.
*   To whom correspondence should be addressed at Brigham and Women's Hospital, Room 703, Thorn Research Building, 20 Shattuck Street, Boston, MA 02115, USA.


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Promigratory Effect of Plasminogen Activator Inhibitor-1 on Invasive Breast Cancer Cell Populations.
B. Chazaud, R. Ricoux, C. Christov, A. Plonquet, R. K. Gherardi, and G. Barlovatz-Meimon (2002)
Am. J. Pathol. 160, 237-246
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Down-regulation of Integrin alpha vbeta 3 Expression and Integrin-mediated Signaling in Glioma Cells by Adenovirus-mediated Transfer of Antisense Urokinase-type Plasminogen Activator Receptor (uPAR) and Sense p16 Genes.
Y. Adachi, S. S. Lakka, N. Chandrasekar, N. Yanamandra, C. S. Gondi, S. Mohanam, D. H. Dinh, W. C. Olivero, M. Gujrati, T. Tamiya, et al. (2001)
J. Biol. Chem. 276, 47171-47177
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Pleiotrophic Inhibition of Pericellular Urokinase-type Plasminogen Activator System by Endogenous Tumor Suppressive Maspin.
H. Biliran Jr. and S. Sheng (2001)
Cancer Res. 61, 8676-8682
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Adhesion receptors of vascular smooth muscle cells and their functions.
E. P. Moiseeva (2001)
Cardiovasc Res 52, 372-386
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Urokinase Receptors Promote beta 1 Integrin Function through Interactions with Integrin alpha 3beta 1.
Y. Wei, J. A. Eble, Z. Wang, J. A. Kreidberg, and H. A. Chapman (2001)
Mol. Biol. Cell 12, 2975-2986
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