Abstract
The integrin alphavbeta6 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 beta6 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 alphavbeta6-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 alphavbeta6, but none of the mutants examined interfered with alphavbeta6-mediated cell adhesion or with localization of alphavbeta6 to focal adhesions. These findings suggest that residues contained within the sequence EKXKVDL are critical for the effects of alphavbeta6 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.
Highlights
Most integrin  subunit cytoplasmic domains contain a highly conserved region of 48 amino acids containing subdomains that have been shown to be critical for localization to focal adhesions and for interaction with cytoplasmic signaling proteins such as the focal adhesion kinase and paxillin [7,8,9,10]
Cytoplasmic domain contains a completely unique 11-amino acid carboxyl-terminal extension. We found that this unique carboxyl-terminal extension was not required for localization of ␣v6 to focal adhesions nor for ␣v6-mediated cell adhesion to fibronectin [6]
Deletions within the Carboxyl-terminal 11 Amino Acids Are Well Expressed on the Cell Surface and Do Not Impair ␣v6mediated Cell Adhesion or Localization of the Receptor to Focal Adhesions—We have previously reported that heterologous expression of the integrin ␣v6 augments proliferation of SW480 cells in three-dimensional collagen gels and that a unique region of the 6 cytoplasmic domain is required for this effect [6]
Summary
Most integrin  subunit cytoplasmic domains contain a highly conserved region of 48 amino acids containing subdomains that have been shown to be critical for localization to focal adhesions and for interaction with cytoplasmic signaling proteins such as the focal adhesion kinase and paxillin [7,8,9,10]. In addition to containing this highly conserved region, the 6. We found that this unique carboxyl-terminal extension was not required for localization of ␣v6 to focal adhesions nor for ␣v6-mediated cell adhesion to fibronectin [6]. Deletion of this region completely abrogated ␣v6-mediated proliferation, both in three-dimensional culture and in nude mice [6]. We have utilized smaller deletions and saturation alanine substitution mutagenesis within this region to map the amino acids responsible for this specific effect of ␣v6 in more detail
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