Division of labor among the alpha 6 beta 4 integrin, beta 1 integrins, andan E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells

Contact of cultured mammary epithelial cells with the basement membrane pro tein laminin induces multiple responses, including cell shape changes, grow th arrest, and, in the presence of prolactin, transcription of the milk pro tein beta-casein. We sought to identify the specific laminin receptor(s) me diating the multiple cell responses to laminin. Using assays with clonal ma mmary epithelial cells, we reveal distinct functions for the alpha 16 beta 4 integrin, beta 1 integrins, and an E3 laminin receptor. Signals from lami nin for beta-casein expression were inhibited in the presence of function-b locking antibodies against both the alpha 6 and pi integrin subunits and by the laminin E3 fragment. The alpha 6-blocking antibody perturbed signals m ediated by the alpha 6 beta 4 integrin, and the beta 1-blocking antibody pe rturbed signals mediated by another integrin, the a subunit(s) of which rem ains to be determined. Neither alpha 6- nor beta 1-blocking antibodies pert urbed the cell shape changes resulting from cell exposure to laminin. Howev er, the E3 laminin fragment and heparin both inhibited cell shape changes i nduced by laminin, thereby implicating an E3 laminin receptor in this funct ion. These results elucidate the multiplicity of cell-extracellular matrix interactions required to integrate cell structure and signaling and ultimat ely permit normal cell function.