The β3 integrin cytoplasmic tail: protein scaffold and control freak

Summary.  Platelet integrin αIIbβ3 plays an essential role in thrombus formation through interactions with adhesive ligands. Successful parenteral blockade of these interactions has validated αIIbβ3 as a therapeutic target in cardiovascular medicine. However, oral αIIbβ3 antagonists have not been successful and there is an unmet need for more effective anti‐platelet drugs. Growing evidence points to the cytoplasmic tails of αIIb and β3, and the β3 tail in particular, as scaffolds for intracellular proteins that mediate inside‐out signaling and regulate αIIbβ3 affinity for ligands. Intracellular protein interactions with the integrin cytoplasmic tails also regulate outside‐in signals to the actin cytoskeleton. Here we focus on recent studies that illustrate the relevance of the β3 cytoplasmic tail as a regulatory scaffold in vivo . We speculate that this scaffold or its interacting proteins may serve as therapeutic targets for the development of future anti‐thrombotic drugs.