Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling.

ABSTRACT: Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the alpha and beta subunit transmembrane domains are associated, ligand binding promotes dissociation and separation of these domains. Here we address whether such separation is required for outside-in signaling. By introduction of an intersubunit disulfide bond, we generated mutant integrin alphaIIbbeta3 with blocked transmembrane separation that binds ligand, mediates adhesion, adopts an extended conformation after ligand binding, and forms antibody-induced macroclusters on the cell surface similarly to wild type. However, the mutant integrin exhibits a profound defect in adhe

SUBMITTER: Zhu J 

PROVIDER: S-EPMC1988953 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature