Identification of a sequence within the integrin beta 6 subunit cytoplasmic domain that is required to support the specific effect of alpha v beta 6 on proliferation in three-dimensional culture

The integrin alpha v beta 6 augments the proliferation of epithelial cells in collagen gels and in vivo. This effect depends on the presence of a unique carboxyl-terminal region of the beta 6 subunit cytoplasmic domain. In the present study, we have utilized deletional and alanine substitution mutagenesis within this region to map the amino acids responsible for alpha v beta 6-mediated proliferation in more detail, Replacement or deletion of any of 6 amino acids (glutamic acid 778, lysine 779, lysine 781, valine 782, aspartic acid 783, and leucine 784) largely abolished the proliferative effects of alpha v beta 6, but none of the mutants examined interfered with alpha v beta 6-mediated cell adhesion or with localization of alpha v beta 6 to focal adhesions, These findings suggest that residues contained within the sequence EKXKVDL are critical for the effects of alpha v beta 6 on proliferation in collagen gels and that pathways initiated by interaction with this sequence are distinct from those required for integrin-mediated cell attachment or focal adhesion formation.