The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others.
The integrin heterodimer VLA-2, previously known as a collagen receptor, is now shown also to be a laminin receptor. Adhesion of the human melanoma cell line LOX to laminin was inhibited by anti-VLA alpha 2 antibodies. Because VLA-2-mediated LOX cell attachment to laminin was not inhibited by digestion with collagenase, collagen contamination of laminin was not a factor. In addition, VLA-2 from LOX cells bound to immobilized laminin, and binding was disrupted by EDTA but not by Arg-Gly-Asp (RGD) peptides. VLA-3 also bound to laminin-Sepharose, although less avidly than VLA-2. Thus, at least four separate members of the integrin beta 1 subfamily serve as laminin receptors--i.e., VLA-2 and VLA-3 (this study) together with VLA-1 and VLA-6 (other reports). Whereas LOX and other cell lines used VLA-2 as both a laminin and collagen receptor, fibroblast VLA-2 mediated collagen but not laminin binding. Likewise, VLA-2 from platelets did not interact with laminin. Despite this functional discordancy, VLA-2 from laminin-binding and nonbinding sources was indistinguishable by all immunochemical and biochemical criteria examined. Thus, functional differences in VLA-2 may be due to cell type-specific modulation.
Elices
M J
MJ
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Hemler
M E
ME
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011946:Receptors, Antigen / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D038981:Receptors, Collagen; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D017474:Receptors, Laminin
D000911:Antibodies, Monoclonal; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D011946:Receptors, Antigen; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D011971:Receptors, Immunologic; D017474:Receptors, Laminin; D003094:Collagen