Skip to main content
Figure 4 | Journal of Hematology & Oncology

Figure 4

From: The unfolded von Willebrand factor response in bloodstream: the self-association perspective

Figure 4

Proposed mechanism of associated vWF activating GPIIb/IIIα. Lateral associated vWF are formed by different multi-vWF through disulfide bond. Associated vWF binds to GPIb-IX-V through A1 domain (in yellow), leading to a shift of GPIIb/IIIa conformation from a low-affinity to high affinity. After the conformation alteration, activated GPIIb/IIIa binds to the C domain (in red) of associated vWF by RGDS within C domain. The generally known signaling pathway from GPIb-IX-V to GPIIb/IIIa is shown in the left platelet which depends on the out-inside and inside-out signaling. Here we have depicted the events subsequent to the interaction between vWF and GPIb-IX-V. The activated GPIb-IX-V subsequently increases the level of intracellular calcium, which is regulated by PLCγ2 derived second messengers inositol 1,4,5 trisphosphate (IP3) and diacylglycerol (DAG). The elevated Ca2+ and DAG together increase CalDAG-GEFI activity that in turn activates RapIb. This leads to the formation of an “activation complex” consisting of RapI, RIAM and talin, which finally cooperates with kindlin3 to activate GPIIb/IIIa. Another possible pathway from GPIb-IX-V to GPIIb/IIIa is shown in the right platelet. On the other hand, lipid rafts may serve as a platform to concentrate activated GPIb-IX-V and GPIIb/IIIa in their respective local membrane when vWF self-association occurs. The formation of lipid rafts is required for out-inside signaling in contrast with the activation of receptor itself by ligand only. They can change the recruitment of these intracelluar receptors and their adaptor proteins in close proximity manner.

Back to article page