title: Calcium as a potential physiological regulator of integrin-mediated cell adhesion.
abstract: alpha v beta 1 and alpha v beta 3 are two related members of the integrin family of cell surface receptors both of which interact with their ligands through the Arg-Gly-Asp recognition sequence, alpha v beta 1 and alpha v beta 3 share the same cation-binding subunit, alpha v, suggesting a similar cation requirement for both integrins. Instead, we observed that Ca2+ exerts different effects on their binding function. The attachment of alpha v beta 3-loaded liposomes to vitronectin and the alpha v beta 3-mediated adhesion of U 251 cells to an Arg-Gly-Asp-containing peptide was supported equally well by Ca2+ and Mg2+. However, IMR 32 cells which bind to Arg-Gly-Asp-containing peptides through alpha v beta 1 adhered in Mg2+ but not in Ca2+. In agreement, Ca2+ did not support the attachment of alpha v beta 1-loaded liposomes to the macromolecular ligand fibronectin or the binding of alpha v beta 1 to Gly-Arg-Gly-Asp-Ser-Pro-Lys-Sepharose in affinity chromatography experiments. Furthermore, in the presence of a constant Mg2+ concentration, Ca2+ had opposite effects on the two receptors in that it inhibited the alpha v beta 1-mediated adhesion of IMR 32 cells to the peptide substrate while enhancing alpha v beta 3-mediated adhesion of U251 cells. The Ca2+ effects occurred at physiological cation concentrations and therefore, our data suggest a physiological role for Ca2+ as a regulator of integrin function and indicate a possible involvement of the beta subunits in cation binding.
authors.affiliation: La Jolla Cancer Research Foundation, California 92037.
authors.forename: D
authors.initials: D
authors.lastname: Kirchhofer
authors.forename: J
authors.initials: J
authors.lastname: Grzesiak
authors.forename: M D
authors.initials: MD
authors.lastname: Pierschbacher
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002448:Cell Adhesion; D002460:Cell Line; D002846:Chromatography, Affinity; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000302:isolation & purification / Q000502:physiology*; D008081:Liposomes; D008274:Magnesium / Q000502:physiology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D019096:Vitronectin
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D016023:Integrins; D008081:Liposomes; D009842:Oligopeptides; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid; D008274:Magnesium; D002118:Calcium