Schematic representation of the signaling pathway from an agonist stimulation to integrin activation. CalDAG GEFI, a GDP/GTP exchange factor specific for Rap small G proteins, and protein kinase C (PKC) activated by a receptor-dependent stimulation of phospholipase C. As a result, Rap1*GTP interaction with RIAM protein (not shown) stimulates talin-1 function in the inside-out pathway. Protein kinase C has been implicated in the signaling as well, although the substrates important for the signaling are currently unknown. Talin-1 and Kindlin FERM domain are shown as spheres with 3 subdomains; the intersecting PH domain in Kindlin is shown as the dark-colored segment.