What is integrin signaling? In this cartoon of the platelet membrane interface, arrows labeled 1a and 1b denote inside-out signaling pathways and arrow 2 denotes outside-in signaling pathways. Inside-out signaling increases the affinity (1a) and avidity (1b) of α_IIbβ₃ for ligands such as fibrinogen. Affinity modulation is depicted hypothetically here as a signal-induced rotation of the β₃ subunit to generate and unmask fibrinogen binding sites in the extracellular domains of α_IIbβ₃. Outside-in signaling triggers a number of postligand binding events and these require cooperative signaling between α_IIbβ₃ and agonist receptors (hashed arrow).