Identification of a sequence within the integrin beta6 subunit cytoplasmic domain that is required to support the specific effect of alphavbeta6 on proliferation in three-dimensional culture.
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.
Dixit
R B
RB
Lung Biology Center, Department of Medicine, University of California, San Francisco, California 94143, USA.
Chen
A
A
Chen
J
J
Sheppard
D
D
D000409:Alanine; D000818:Animals; D000951:Antigens, Neoplasm; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D039641:Integrin beta Chains; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D000951:Antigens, Neoplasm; D005353:Fibronectins; D039641:Integrin beta Chains; D016023:Integrins; C073878:integrin alphavbeta6; C072170:integrin beta6; D000409:Alanine