Figure 3.

Inside-out- and outside-in-signaling of integrin α_IIbβ₃. In resting platelets, integrin α_IIbβ₃ is in an inactive conformation that prevents ligand binding. However, an initial activation of platelets (e.g., via GPIb or GPVI signaling) leads to binding of cytosolic kindlin and talin. This binding induces a conformational change of integrin α_IIbβ₃ that allows the binding of fibrinogen and other ligands. The process which induces the conformational change of integrin α_IIbβ₃ is called inside-out signaling. Binding of a ligand like fibrinogen to the extracellular domain of integrin α_IIbβ₃ triggers a signaling cascade through various kinases. This amplifies different platelet processes such as spreading, granule secretion and aggregation. The process of extracellular ligand-induced activation of integrin α_IIbβ₃ is called outside-in signaling. This figure was created using images from Servier Medical Art Commons Attribution 3.0 Unported License. (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License”.