title: A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.
abstract: A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation.
authors.affiliation: Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: J
authors.initials: J
authors.lastname: Ylänne
authors.forename: D
authors.initials: D
authors.lastname: Mandelman
authors.forename: W
authors.initials: W
authors.lastname: Puzon
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism*; D019012:Integrin beta1; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D017354:Point Mutation; D017469:Receptors, Fibronectin / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D009842:Oligopeptides; D017469:Receptors, Fibronectin; C053476:invasin, Yersinia; C047981:arginyl-glycyl-aspartic acid