title: Intercellular adhesion molecule (ICAM)-1, but not ICAM-2, activates RhoA and stimulates c-fos and rhoA transcription in endothelial cells.
abstract: ICAM-1 and -2 are integrin-binding Ig superfamily adhesion molecules that are important for leukocyte transmigration across endothelial monolayers. ICAM-1 cross-linking is known to activate the small GTPase RhoA and induce stress fiber formation in endothelial cells, but ICAM-2 signaling has not been investigated. In this study, we compare ICAM-1 and ICAM-2 signaling and localization in HUVECs. Although ICAM-1 and ICAM-2 both localize with the actin-binding protein moesin in apical microvilli, only ICAM-1 colocalizes with moesin after cross-linking. Unlike ICAM-1, ICAM-2 does not activate RhoA or alter actin cytoskeletal organization. Interestingly, ICAM-1 stimulates transcription of c-fos, a known early response gene. In addition, it up-regulates rhoA expression, suggesting that it activates a positive feedback pathway after RhoA activation. These results indicate that in endothelial cells, ICAM-1, but not ICAM-2, rapidly stimulates signaling responses involving RhoA.
authors.affiliation: Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London, United Kingdom.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Thompson
authors.forename: Anna M
authors.initials: AM
authors.lastname: Randi
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D016762:Genes, fos / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; C065289:ICAM2 protein, human; D007106:Immune Sera; D008840:Microfilament Proteins; D018799:Intercellular Adhesion Molecule-1; C071058:moesin; D020742:rhoA GTP-Binding Protein