Integrin signaling: building connections beyond the focal contact?

The integrin family of adhesion receptors is notable for its bi-directional signaling properties, changing extracellular conformation and ligand binding affinity in response to external agonists, and inducing complex intracellular events following ligation. The interaction of integrins with intracellular or transmembrane moieties has been extensively studied in order to define the mechanisms of bi-directional signaling. In particular, the recruitment of integrins to focal contacts puts them in proximity with many cytoskeletal and signaling molecules. The importance of these structures in connecting integrins and signaling pathways has been well described. However, the purpose of this minireview is to explore additional protein interactions and how these might serve as an alternative means in connecting integrins and signaling pathways.