14-3-3 protein zeta – integrin beta-3 complex (14-3-3ζ–ITGB3 complex)

14-3-3ζ (YWHAZ) is an adapter protein that serves as a critical node in platelet signaling by physically linking the Glycoprotein Ib-IX-V (GPIb-IX) complex and the integrin αIIbβ3 (GPIIb/IIIa) (Shen et al., 2000; Gong et al., 2010). This interaction is essential for "outside-in" signaling, where the binding of ligands like von Willebrand factor (vWF) or fibrinogen to surface receptors triggers intracellular pathways that promote platelet spreading, stable adhesion, and thrombus growth (Dai et al., 2005). Specifically, 14-3-3ζ binds to the C-terminal tails of GPIbα and the integrin β3 subunit, facilitating the recruitment of signaling molecules such as c-Src and phosphoinositide 3-kinase (PI3K). In pathological states, this signaling axis drives the formation of occlusive arterial thrombi, leading to myocardial infarction and stroke. Because this interaction is primarily involved in thrombus stabilization rather than the initial hemostatic response, it is considered a high-value target for developing antithrombotic therapies with reduced bleeding risks. Experimental agents like the peptide MPα-tide have shown efficacy in disrupting this complex and preventing thrombosis in vivo without significantly impairing normal hemostasis (Wang et al., 2014).

Other names

14-3-3ζ-integrin β3 complexGPIb-IX-14-3-3ζ-integrin β3 signaling axisYWHAZ-ITGB3 complexPlatelet 14-3-3ζ-integrin β3 interaction

Inhibition of protein-protein interaction (PPI) between 14-3-3ζ and the cytoplasmic tails of integrin β3 and GPIbα, preventing outside-in signaling and stable thrombus formation.