Regulation of cell migration by the integrin beta subunit ectodomain.
CS-1 melanoma cells transfected with cDNAs encoding either the beta 3 or beta 5 integrin subunit protein express alpha v beta 3 or alpha v beta 5, respectively, enabling them to adhere to vitronectin yet only alpha v beta 3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, alpha v beta 5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric beta subunit proteins, in which the ecto- and cytoplasmic domains of beta 3 and beta 5 were exchanged (termed alpha v beta 3/5 or alpha v beta 5/3). Surprisingly, alpha v beta 3/5 expressing cells spread and migrate on vitronectin while cells expressing alpha v beta 5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin beta subunit.
Filardo
E J
EJ
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Deming
S L
SL
Cheresh
D A
DA
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D006801:Humans; D039641:Integrin beta Chains; D039661:Integrin beta3; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015394:Molecular Structure; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011487:Protein Conformation; D019030:Receptors, Vitronectin / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
D015703:Antigens, CD; D039641:Integrin beta Chains; D039661:Integrin beta3; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; C064660:integrin alphaVbeta5; C084344:integrin beta5