The integrin alpha 6 beta 4 is a laminin receptor.
In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1.
Lee
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EC
Laboratory of Cancer Biology, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Lotz
M M
MM
Steele
G D
GD
Mercurio
A M
AM
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002846:Chromatography, Affinity; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D017474:Receptors, Laminin; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016023:Integrins; D007797:Laminin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin