![Fig. 7. Schematic representation of the mechanisms of platelet activation by immobilized VWF under shear stress. / A1 and A3 are the VWF domains that interact with platelet GPIbα and fibrillar collagen, respectively. The A1 domain also interacts with the nonfibrillar collagen type VI.23 The sequence RGD in the VWF C1 domain interacts with activated αIIbβ3. PIP2 indicates phosphatidyl-inositol-4,5-bisphosphate; IP3, inositol-1,4,5-trisphosphate; DG, diacylglycerol; PKC, protein kinase C; and PI3-K = phosphatidylinositol 3-kinase. ADP is shown interacting with two 7-transmembrane-domain, G-protein–coupled receptors: P2Y1, linked to Ca++ release from internal stores, and P2Y12, linked to the regulation of adenylyl cyclase activity. The position of α/β and γ [Ca++]i peaks relative to GPIb-IX-V engagement by A1VWF and signal amplification by ADP and PI3-K, respectively, differs from the previous interpretation by Yap et al.15 Also, an increase in cAMP and cGMP levels blocked the first Ca++ response linked to GPIb-IX-V stimulation (that is, α/β peaks) and consequently other downstream activation events.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/100/8/10.1182_blood-2002-02-0514/4/h82023252007.jpeg?Expires=1724268200&Signature=qpBc0e2-7YT69Si~DAReSwP2xcFOVZ-P2-KYjRvo7~fZk3MaXnmxu1KAddvIV2GdylA51RXM1Az5ejAkwmM46Mq~pd0EiLq3A2zf3~km3JljNPy8PMaKtgke0I3t7dHgsUpXEItr8Ekt87yVwkXXUbJ~cvrrrRzLtwIMHi~twZ1aOlH2L-hyQJeIUSrneQA63e31h0EJnk34VpHh5J4kODK2bkvVkxDPFAaIK7MaGvk7MIrkdQbQjVnqFuJATIqrct2ZI6yUQk5OsMNeCcR9KWAOFyn52eCvTfiENlCvhknQMIlNzP~weCYa-n4r7f3Kn5U7eonJpnEghpPq9GUPPg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Schematic representation of the mechanisms of platelet activation by immobilized VWF under shear stress.
A1 and A3 are the VWF domains that interact with platelet GPIbα and fibrillar collagen, respectively. The A1 domain also interacts with the nonfibrillar collagen type VI.23 The sequence RGD in the VWF C1 domain interacts with activated αIIbβ3. PIP2 indicates phosphatidyl-inositol-4,5-bisphosphate; IP3, inositol-1,4,5-trisphosphate; DG, diacylglycerol; PKC, protein kinase C; and PI3-K = phosphatidylinositol 3-kinase. ADP is shown interacting with two 7-transmembrane-domain, G-protein–coupled receptors: P2Y1, linked to Ca++ release from internal stores, and P2Y12, linked to the regulation of adenylyl cyclase activity. The position of α/β and γ [Ca++]i peaks relative to GPIb-IX-V engagement by A1VWF and signal amplification by ADP and PI3-K, respectively, differs from the previous interpretation by Yap et al.15 Also, an increase in cAMP and cGMP levels blocked the first Ca++ response linked to GPIb-IX-V stimulation (that is, α/β peaks) and consequently other downstream activation events.
