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Vol. 10, Issue 9, 2817-2828, September 1999

Division of Labor among the alpha 6beta 4 Integrin, beta 1 Integrins, and an E3 Laminin Receptor to Signal Morphogenesis and beta -Casein Expression in Mammary Epithelial Cells

John Muschler,*dagger André Lochter,Dagger Calvin D. Roskelley,§ Peter Yurchenco,parallel and Mina J. Bissell*

 *Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720;  Dagger Center for Clinical and Basic Research, Ballerup, Denmark;  §Department of Anatomy, University of British Columbia, Vancouver, British Columbia, Canada; and  parallel Department of Pathology, Robert Woods Johnson Medical School, Piscataway, New Jersey 08854

Contact of cultured mammary epithelial cells with the basement membrane protein laminin induces multiple responses, including cell shape changes, growth arrest, and, in the presence of prolactin, transcription of the milk protein beta -casein. We sought to identify the specific laminin receptor(s) mediating the multiple cell responses to laminin. Using assays with clonal mammary epithelial cells, we reveal distinct functions for the alpha 6beta 4 integrin, beta 1 integrins, and an E3 laminin receptor. Signals from laminin for beta -casein expression were inhibited in the presence of function-blocking antibodies against both the alpha 6 and beta 1 integrin subunits and by the laminin E3 fragment. The alpha 6-blocking antibody perturbed signals mediated by the alpha 6beta 4 integrin, and the beta 1-blocking antibody perturbed signals mediated by another integrin, the alpha  subunit(s) of which remains to be determined. Neither alpha 6- nor beta 1-blocking antibodies perturbed the cell shape changes resulting from cell exposure to laminin. However, the E3 laminin fragment and heparin both inhibited cell shape changes induced by laminin, thereby implicating an E3 laminin receptor in this function. These results elucidate the multiplicity of cell-extracellular matrix interactions required to integrate cell structure and signaling and ultimately permit normal cell function.


dagger    Corresponding author. E-mail address: jlmuschler{at}lbl.gov.


Molecular Biology of the Cell
Vol. 10, 2817-2828, September 1999
Copyright © 1999 by The American Society for Cell Biology



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