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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actin Cytoskeleton / metabolism
-
Actins / metabolism
-
Antigens, CD / immunology
-
Antigens, CD / metabolism
-
Antigens, CD / physiology*
-
Cell Adhesion Molecules / immunology
-
Cell Adhesion Molecules / metabolism
-
Cell Adhesion Molecules / physiology*
-
Cells, Cultured
-
Cross-Linking Reagents / metabolism
-
Endothelium, Vascular / cytology*
-
Endothelium, Vascular / metabolism*
-
Gene Expression Regulation* / immunology
-
Genes, fos* / immunology
-
Humans
-
Immune Sera / metabolism
-
Immune Sera / pharmacology
-
Intercellular Adhesion Molecule-1 / immunology
-
Intercellular Adhesion Molecule-1 / metabolism
-
Intercellular Adhesion Molecule-1 / physiology*
-
Microfilament Proteins / metabolism
-
Transcription, Genetic* / immunology
-
rhoA GTP-Binding Protein / biosynthesis
-
rhoA GTP-Binding Protein / genetics
-
rhoA GTP-Binding Protein / metabolism*
Substances
-
Actins
-
Antigens, CD
-
Cell Adhesion Molecules
-
Cross-Linking Reagents
-
ICAM2 protein, human
-
Immune Sera
-
Microfilament Proteins
-
Intercellular Adhesion Molecule-1
-
moesin
-
rhoA GTP-Binding Protein