Regulation of T-cell antigen receptor-mediated inside-out signaling by cytosolic adapter proteins and Rap1 effector molecules

Integrins are critical for the migration of T cells to lymphoid organs and to sites of inflammation and are also necessary for productive interactions between T cells and antigen-presenting cells. Integrin activation is enhanced following T-cell receptor (TCR) engagement, as signals initiated by the TCR increase affinity and avidity of integrins for their ligands. This process, known as inside-out signaling, has been shown to require several molecular components including the cytosolic adapter proteins adhesion and degranulation-promoting adapter protein and Src homology 2 domain-containing adapter protein of 55 kDa, the low molecular weight guanosine triphosphatase Rap1, and the Rap1 effector proteins Rap1 guanosine triphosphate-interacting adapter molecule, regulator of adhesion and cell polarization enriched in lymphoid tissues, and protein kinase D1. Herein, we review recent findings about how the TCR is linked to integrin activation through inside-out signaling.