PathwayStep564 PathwayStep565 PathwayStep566 PathwayStep567 PathwayStep568 PathwayStep569 PathwayStep570 GPIb-IX-V binding to 14-3-3 zeta is reduced by shear stress GP1b signaling involves c-Src c-Src binds Raf1 14-3-3-zeta binds Raf1 GP1b-IX-V binds filamin GP1b-IX-V:13-3-3-zeta complexes with p85 PI3K GP1b-IX-V binds 14-3-3-zeta GP1b-IX-V activation signalling Authored: Akkerman, JW, 2009-06-03 Edited: Jupe, S, 2010-06-07 Pubmed11001899 Pubmed15507277 Pubmed17585075 Pubmed17597991 Pubmed2424116 Reactome Database ID Release 43430116 Reactome, http://www.reactome.org ReactomeREACT_23847 Reviewed: Kunapuli, SP, 2010-06-07 The platelet GPIb complex (GP1b-IX-V) together with GPVI are primarily responsible for regulating the initial adhesion of platelets to the damaged blood vessel and platelet activation. The importance of GPIb is demonstrated by the bleeding problems in patients with Bernard-Soulier syndrome where this receptor is either absent or defective. GP1b-IX-V binds von Willebrand Factor (vWF) to resting platelets, particularly under conditions of high shear stress. This transient interaction is the first stage of the vascular repair process. Activation of GP1b-IX-V on exposure of the fibrous matrix following atherosclerotic plaque rupture, or in occluded arteries, is a major contributory factor leading to thrombus formation leading to heart attack or stroke. GpIb also binds thrombin (Yamamoto et al. 1986), at a site distinct from the site of vWF binding, acting as a docking site for thrombin which then activates Proteinase Activated Receptors leading to enhanced platelet activation (Dormann et al. 2000).