Molecular mechanisms of platelet adhesion and activation.
When a blood vessel is injured, control of bleeding starts with the rapid adhesion of circulating platelets to the site of damage. Within seconds, the adhered platelets are activated, secrete the contents of storage organelles, spread out over the damaged area and recruit more platelets to the developing thrombus. However, if this same process occurs in a diseased, sclerotic or occluded vessel, the resulting platelet thrombus may break away and block the coronary artery, causing a heart attack, or restrict blood supply to the brain, causing a stroke. The glycoprotein (GP) Ib-IX-V complex, a member of the leucine-rich protein family, is a constitutive platelet membrane receptor for von Willebrand Factor (vWF), a multimeric adhesive glycoprotein found in the matrix underlying the endothelial cell lining of the blood vessel wall and in the plasma. Binding of vWF to the GP. Ib-IX-V complex regulates adhesion of platelets to the subendothelium at high shear flow, and initiates signal transduction leading to platelet activation. The GP Ib-IX-V complex also constitutes a binding site for alpha-thrombin, an interaction that facilitates thrombin-dependent platelet activation. This review will focus on recent detailed analysis of the GP Ib-IX-V complex and vWF that has identified discrete amino acid sequences that mediate their interaction. An anionic/sulfated tyrosine sequence of the GP Ib alpha-chain that is critical for binding of the GP Ib-IX-V complex to both vWF and alpha-thrombin is analogous to sulfated anionic amino acid sequences mediating interactions of other adhesive proteins, including P-selectin binding to PSGL-1 and Factor VIII binding to vWF.
Andrews
R K
RK
Hazel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
López
J A
JA
Berndt
M C
MC
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015539:Platelet Activation / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000502:physiology; D013431:Sulfates / Q000378:metabolism; D013917:Thrombin / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019038:Platelet Glycoprotein GPIb-IX Complex; D013431:Sulfates; D014841:von Willebrand Factor; D013917:Thrombin