Aggregin: a platelet ADP receptor that mediates activation.
ADP is known to induce platelet shape change, aggregation, and exposure of fibrinogen binding sites as well as inhibit stimulated adenylate cyclase. The platelet is unique in that its purinergic receptor prefers ADP over ATP, which functions as a competitive antagonist. The affinity reagent, 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), has been used to covalently label a single membrane protein, aggregin, on the external platelet surface with mol wt of 100 kDa. Concomitant with incorporation of FSBA, ADP-induced shape change, aggregation, and fibrinogen binding is inhibited. FSBA is also a weak agonist at short times and high concentration, which suggests that prior noncovalent binding to aggregin takes place before covalent modification. Aggregin differs from platelet glycoprotein IIIa in its physical and immunochemical properties. Aggregin is distinct from the receptor coupled to adenylate cyclase. Using FSBA as a probe, platelet aggregation by thromboxane A2 analogs and collagen was shown to be dependent on ADP but not the shape change induced by these agonists. Binding to aggregin is required for epinephrine-induced aggregation. In turn, epinephrine increases the affinity of ADP for its receptor. Thrombin at concentrations greater than 2 nM (0.2 units/ml) stimulates platelet aggregation independent of ADP, but by raising cytoplasmic Ca2+ it activates platelet calpain, which in turn cleaves aggregin. Thus aggregin, in addition to serving as the ADP receptor linked to shape change and aggregation, plays a role in fibrinogen receptor latency that is relieved entirely by ADP binding to or proteolysis of aggregin.
Colman
R W
RW
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000345:Affinity Labels; D003094:Collagen / Q000502:physiology; D004837:Epinephrine / Q000502:physiology; D006801:Humans; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011983:Receptors, Purinergic / Q000097:blood / Q000502:physiology*; D013917:Thrombin / Q000502:physiology; D013928:Thromboxane A2 / Q000502:physiology
D000345:Affinity Labels; D010980:Platelet Membrane Glycoproteins; D011983:Receptors, Purinergic; C055422:aggregin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine