2001
DOI: 10.1073/pnas.98.4.1823
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A thrombin receptor function for platelet glycoprotein Ib–IX unmasked by cleavage of glycoprotein V

Abstract: Glycoprotein (GP) V is a major substrate cleaved by the protease thrombin during thrombin-induced platelet activation. Previous analysis of platelets from GP V-null mice suggested a role for GP V as a negative modulator of platelet activation by thrombin. We now report the mechanism by which thrombin activates GP V ؊͞؊ platelets. We show that proteolytically inactive forms of thrombin induce robust stimulatory responses in GP V null mouse platelets, via the platelet GP Ib-IX-V complex. Because proteolytically … Show more

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Cited by 161 publications
(130 citation statements)
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“…A prediction from this model is that part of the platelet-bound thrombin should be found in lipid rafts, along with the other components of this enzyme-cofactor-substrate complex. Recently, cleavage of GPV by thrombin has been shown to play a signaling role in platelet activation (57). Whether the cleavage of GPV also facilitates the exposure of the FXI-binding site in the GPIb-IX-V complex remains to be tested.…”
Section: I-ppack-thrombin To Glycocalicin In the Presence Of Various mentioning
confidence: 99%
See 1 more Smart Citation
“…A prediction from this model is that part of the platelet-bound thrombin should be found in lipid rafts, along with the other components of this enzyme-cofactor-substrate complex. Recently, cleavage of GPV by thrombin has been shown to play a signaling role in platelet activation (57). Whether the cleavage of GPV also facilitates the exposure of the FXI-binding site in the GPIb-IX-V complex remains to be tested.…”
Section: I-ppack-thrombin To Glycocalicin In the Presence Of Various mentioning
confidence: 99%
“…Access to the active site is restricted by two surface loops, the 50-insertion loop (Leu 45 -Asn 57 , thrombin B chain numbering system) and the autolysis loop (Leu 144 -Gly 155 ), that are situated on the northern and southern rims of the active-site cleft, respectively. Enzyme specificity is further defined by two ligand-binding sites (exosites) that are characterized by a high density of solvent-exposed basic residues.…”
mentioning
confidence: 99%
“…This represents a high affinity receptor for thrombin, and a mounting body of evidence indicates that it may contribute to the activation of platelets (32)(33)(34)(35)(36)(37). It has been known for years that platelets from patients affected by the Bernard-Soulier syndrome, which lack GPIb-IX-V, show impaired response to thrombin (38).…”
mentioning
confidence: 99%
“…These data imply that different signaling pathways could be involved in the activation induced by thrombin or TRAP, a concept that seems to be accepted in additional literature. 2,30 It may be argued that the differences noted in our activation studies could be related to the difficulty in achieving equivalent concentrations with the two activating agents. It is worth mentioning that concentrations of thrombin or TRAP that induced similar aggregating responses (ie, 0.1 U/ml of thrombin and 30 mol/L of TRAP) caused equivalent levels of secretion and of phosphorylation of those proteins present in whole platelet lysates, but still induced differential intensity of phosphorylation of proteins associated with the insoluble cytoskeletal fractions.…”
Section: Discussionmentioning
confidence: 98%
“…Both receptors seem to act simultaneously although independently. 2,30 However, the ultrastructural features observed with TRAP do not seem to be physiological. Our present study further supports these concepts.…”
Section: Discussionmentioning
confidence: 99%