Endothelial cells use alpha 2 beta 1 integrin as a laminin receptor.
Human umbilical vein endothelial cells attach and spread on laminin-coated substrates. Affinity chromatography was used to identify the attachment receptor. Fractionation of extracts from surface-iodinated endothelial cells on human laminin-Sepharose yielded a heterodimeric complex, the subunits of which migrated with molecular sizes corresponding to 160/120 kD and 160/140 kD under nonreducing and reducing conditions, respectively. The purified receptor bound to laminin and slightly less to fibronectin and type IV collagen in a radioreceptor assay. This endothelial cell laminin receptor was classified as an alpha 2 beta 1 integrin because monoclonal and polyclonal antibodies directed against the alpha 2 and bet 1 subunits immunoprecipitated the receptor. Cytofluorometric analysis and immunoprecipitation showed that the alpha 2 subunit is an abundant integrin alpha subunit in the endothelial cells and that the alpha subunits associated with laminin binding in other types of cells are expressed in these cells only at low levels. The alpha 2 beta 1 integrin appears to be a major receptor for laminin in the endothelial cells, because an anti-alpha 2 monoclonal antibody inhibited the attachment of the endothelial cells to human laminin. These results define a new role for the alpha 2 subunit in laminin binding and suggest that the ligand specificity of the alpha 2 beta 1 integrin, which is known as a collagen receptor in other types of cells, can be modulated by cell type-specific factors to include laminin binding.
Languino
L R
LR
La Jolla Cancer Research Foundation, California 92037.
Gehlsen
K R
KR
Wayner
E
E
Carter
W G
WG
Engvall
E
E
Ruoslahti
E
E
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002846:Chromatography, Affinity; D003094:Collagen; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D005353:Fibronectins; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000276:immunology* / Q000302:isolation & purification; D007700:Kinetics; D007797:Laminin / Q000502:physiology*; D051379:Mice; D011971:Receptors, Immunologic / Q000502:physiology*; D017474:Receptors, Laminin
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin; D003094:Collagen