Role of cholesterol in formation and function of a signaling complex involving alphavbeta3, integrin-associated protein (CD47), and heterotrimeric G proteins.
Integrin-associated protein (CD47) is a multiply membrane spanning member of the immunoglobulin superfamily that regulates some adhesion-dependent cell functions through formation of a complex with alphavbeta3 integrin and trimeric G proteins. Cholesterol is critical for the association of the three protein components of the supramolecular complex and for its signaling. The multiply membrane spanning domain of IAP is required for complex formation because it binds cholesterol. The supramolecular complex forms preferentially in glycosphingolipid-enriched membrane domains. Binding of mAb 10G2 to the IAP Ig domain, previously shown to be required for association with alphavbeta3, is affected by both the multiply membrane spanning domain and cholesterol. These data demonstrate that cholesterol is an essential component of the alphavbeta3/IAP/G protein signaling complex, presumably acting through an effect on IAP conformation.
Green
J M
JM
Center for Host/Pathogen Interactions, University of California, San Francisco, San Francisco, California 94143, USA.
Zheleznyak
A
A
Chung
J
J
Lindberg
F P
FP
Sarfati
M
M
Frazier
W A
WA
Brown
E J
EJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D019699:Thrombospondins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism; D047392:beta-Cyclodextrins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D003505:Cyclodextrins; D000939:Epitopes; D006017:Glycolipids; D019030:Receptors, Vitronectin; D019699:Thrombospondins; D019096:Vitronectin; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D019204:GTP-Binding Proteins