title: Signalling through the platelet glycoprotein Ib-V-IX complex.
abstract: The glycoprotein Ib-V-IX is one of the major adhesive receptors expressed on the surface of circulating platelets. It is composed of four different polypeptides-GPIbalpha, GPIbbeta, GPIX, and GPV-and represents a multifunctional receptor able to interact with a number of ligands, including the adhesive protein von Willebrand factor, the coagulation factors thrombin, factors XI and XII, and the membrane glycoproteins P-selectin and Mac-1. Interaction of GPIb-V-IX with the subendothelial von Willebrand factor is essential for primary haemostasis, as it initiates platelet adhesion to the subendothelial matrix at the sites of vascular injury even under high flow conditions. Upon interaction with von Willebrand factor, GPIb-V-IX initiates transmembrane signalling events for platelet activation, which eventually result in integrin alpha(IIb)beta(3) stimulation and platelet aggregation. The investigation of the biochemical mechanisms for platelet activation by GPIb-V-IX has attracted increasing attention during the last years. This review will describe and discuss recent findings that have provided new insights into the events underlying GPIb-V-IX transmembrane signalling. In particular, it will summarise basic concepts on the structure of this receptor, extracellular ligands, and intracellular interactors potentially involved in transmembrane signalling. The recently suggested role of membrane Fc receptors in GPIb-V-IX-initiated platelet activation will also be discussed, along with the involvement of lipid metabolising enzymes, tyrosine kinases, and the cytoskeleton in the crosstalk between GPIb-V-IX and integrin alpha(IIb)beta(3).
authors.affiliation: Center of Excellence for Applied Biology, Department of Biochemistry, University of Pavia, via Bassi 21, Pavia 27100, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Canobbio
authors.forename: Cesare
authors.initials: C
authors.lastname: Balduini
authors.forename: Mauro
authors.initials: M
authors.lastname: Torti
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008954:Models, Biological; D010741:Phospholipases A / Q000737:chemistry; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000096:biosynthesis* / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry*; D011485:Protein Binding; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000737:chemistry; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D008024:Ligands; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C032193:glycoprotein receptor GPIb-IX; D014841:von Willebrand Factor; D010741:Phospholipases A; D010738:Type C Phospholipases