Regulation of VLA-4 integrin affinity and conformation by G protein-coupled receptor signaling pathways

From Q-bio

Regulation of VLA-4 integrin affinity and conformation by G protein-coupled receptor signaling pathways

Larry A. Sklar and Alexandre Chigaev Cancer Center and New Mexico Molecular Libraries Screening Center University of New Mexico HSC, Albuquerque, NM, USA, 87131

Rapid activation of integrins in response to GPCR-induced signaling serves as a basis for leukocyte adhesion on vascular endothelium. Current models of integrin activation include increased affinity for ligand, molecular extension, ligand induced binding sites, etc. We have developed quantitative real-time flow cytometric methods to evaluate the roles of affinity and conformation in cell adhesion and ligand binding. Recent work has suggested, that rather than being intrinsically related to the affinity state of the ligand binding pocket, VLA-4 integrin conformation can be independently regulated by specific signaling pathways as well as novel small molecules. While affinity regulates the duration of adhesion, molecular extension regulates the efficiency of adhesion and access to intermolecular binding partners.

Supported by NIH R01 HL081062 and U54 MH074425 (to L.A.S.), Leukemia and Lymphoma Society Grant 7388-06 (to L.A.S.), and C-2297-RAC grant from Dedicated Health Research Funds of the University of New Mexico School of Medicine (to A.C.).