Rap1 Translates Chemokine Signals to Integrin Activation, Cell Polarization, and Motility across Vascular Endothelium under Flow

• Published in: The Journal of cell biology Vol. 161; no. 2; pp. 417 - 427
• Main Authors: Shimonaka, Mika, Katagiri, Koko, Nakayama, Toshinori, Fujita, Naoya, Tsuruo, Takashi, Yoshie, Osamu, Kinashi, Tatsuo
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 28.04.2003; The Rockefeller University Press
• Subjects: Adenoviruses; Animals; Blood vessels; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Polarity - drug effects; Cell Polarity - physiology; Cells, Cultured; Chemokine CCL21; Chemokine CXCL12; Chemokines; Chemokines - metabolism; Chemokines, CC - metabolism; Chemokines, CC - pharmacology; Chemokines, CXC - metabolism; Chemokines, CXC - pharmacology; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - physiology; Endothelial cells; Endothelium, Vascular - metabolism; GTPase-Activating Proteins; Hemodynamics - drug effects; Hemodynamics - physiology; Human migration; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Integrins; Integrins - metabolism; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Leukocytes; Lymphatic system; Lymphocyte Function-Associated Antigen-1 - metabolism; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Mice; Mice, Inbred BALB C; Molecules; Nuclear Proteins - metabolism; Nuclear Proteins - pharmacology; rap1 GTP-Binding Proteins - antagonists & inhibitors; rap1 GTP-Binding Proteins - genetics; rap1 GTP-Binding Proteins - metabolism; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Shear stress; Signal Transduction - drug effects; Signal Transduction - physiology; T lymphocytes; Transmigration; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism

Chemokines arrest circulating lymphocytes within the vasculature through the rapid up-regulation of leukocyte integrin adhesive activity, promoting subsequent lymphocyte transmigration. However, the key regulatory molecules regulating this process have remained elusive. Here, we demonstrate that Rap...