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Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR Protease-activated receptor 3 is a second thrombin receptor in humans. Nature. 386:1997;502-506.
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A dual thrombin receptor system for platelet activation
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In this landmark study, not only is the par-3 knockout mouse described but the sequence of par-4 is reported. The importance of PAR-3 and PAR-4 on murine platelets and PAR-4 on human platelets is delineated.
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Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV.Jr., Tam C, Coughlin SR A dual thrombin receptor system for platelet activation. Nature. 394:1998;690-694. In this landmark study, not only is the par-3 knockout mouse described but the sequence of par-4 is reported. The importance of PAR-3 and PAR-4 on murine platelets and PAR-4 on human platelets is delineated.
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Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin
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Experiments in this study confirm that together PAR-1 and PAR-4 account for most thrombin signaling in human platelets.
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Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest. 103:1999;879-887. Experiments in this study confirm that together PAR-1 and PAR-4 account for most thrombin signaling in human platelets.
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Stimulation of platelet activation and aggregation by a carboxy-terminal peptide from thrombospondin binding to the integrin-associated protein receptor
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The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi
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The direct physical and functional coupling of a five-transmembrane-spanning protein to the heterotrimeric G protein, Gi is described. This is significant for understanding the mechanism by which thrombospondin stimulates cells and because heterotrimeric G-proteins are most often coupled to seven-transmembrane-spanning proteins.
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Frazier WA, Gao AG, Dimitry J, Chung J, Brown EJ, Lindberg FP, Linder ME The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi. J Biol Chem. 274:1999;8554-8560. The direct physical and functional coupling of a five-transmembrane-spanning protein to the heterotrimeric G protein, Gi is described. This is significant for understanding the mechanism by which thrombospondin stimulates cells and because heterotrimeric G-proteins are most often coupled to seven-transmembrane-spanning proteins.
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Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI
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Glycoprotein VI is a major collagen receptor for platelet activation: It recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not
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Kehrel B, Wierwille S, Clemetson KJ, Anders O, Steiner M, Knight CG, Farndale RW, Okuma M, Barnes MJ Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not. Blood. 91:1998;491-499.
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The Fc receptor γ-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen
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Poole A, Gibbins JM, Turner M, van Vugt MJ, van de Winkel JG, Saito T, Tybulewicz VL, Watson SP The Fc receptor γ-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J. 16:1997;2333-2341.
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3, as defined by acquiring the ability to binding large soluble ligands.
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3, as defined by acquiring the ability to binding large soluble ligands.
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3 signaling in platelets
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Studies with platelets from Syk knockout mice demonstrate that Syk plays a significant but minor role in platelet aggregation induced by ADP (plus or minus epinephrine).
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3 signaling in platelets. Blood. 93:1999;2645-2652. Studies with platelets from Syk knockout mice demonstrate that Syk plays a significant but minor role in platelet aggregation induced by ADP (plus or minus epinephrine).
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Fc receptor-mediated platelet activation is dependent on phosphatidylinositol 3-kinase activation and involves p120(Cbl)
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In this paper the significant contribution of PI3K to Fc receptor-induced platelet activation versus a minor contribution to thrombin-induced activation is noted. In addition, little was known of the role of the adapter protein Cbl in platelet function but here its coupling to the catalytic domain of PI3K and potential role in recruiting PI3K to the Fc receptor is described.
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Saci A, Pain S, Rendu F, Bachelot-Loza C Fc receptor-mediated platelet activation is dependent on phosphatidylinositol 3-kinase activation and involves p120(Cbl). J Biol Chem. 274:1999;1898-1904. In this paper the significant contribution of PI3K to Fc receptor-induced platelet activation versus a minor contribution to thrombin-induced activation is noted. In addition, little was known of the role of the adapter protein Cbl in platelet function but here its coupling to the catalytic domain of PI3K and potential role in recruiting PI3K to the Fc receptor is described.
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Biphasic activation of PKBα/Akt in platelets. Evidence for stimulation both by phosphatidylinositol 3,4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3,4,5-trisphosphate
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Banfic H, Downes CP, Rittenhouse SE Biphasic activation of PKBα/Akt in platelets. Evidence for stimulation both by phosphatidylinositol 3,4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 273:1998;11630-11637.
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Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
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Although platelets were not studied here, the observation that integrin linked kinase (ILK) activity is positioned between PI3K and PKB is a finding of potential significance to platelet function.
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Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA. 95:1998;11211-11216. Although platelets were not studied here, the observation that integrin linked kinase (ILK) activity is positioned between PI3K and PKB is a finding of potential significance to platelet function.
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The identification by these authors of a cytotoxin that selectively inhibits R-Ras should prove useful in determining the role of R-Ras in platelet function.
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3 activation, as had been previously reported. RhoA does contribute, however, to platelet adhesion and focal contact formation.
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3 activation, as had been previously reported. RhoA does contribute, however, to platelet adhesion and focal contact formation.
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Effects of the mitogen-activated protein (MAP) kinase kinase inhibitor 2-(2′-amino-3′-methoxyphenyl)-oxanaphthalen-4-one (PD98059) on human platelet activation
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McNicol A, Philpott CL, Shibou TS, Israels SJ Effects of the mitogen-activated protein (MAP) kinase kinase inhibitor 2-(2′-amino-3′-methoxyphenyl)-oxanaphthalen-4-one (PD98059) on human platelet activation. Biochem Pharmacol. 55:1998;1759-1767.
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0032545497
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The death effector domain of PEA-15 is involved in its regulation of integrin activation
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3 integrin function. PEA-15 is a member of the death effector domain (DED)-containing family of molecules, which were previously only known to function in apoptosis. PEA-15 mediates its rescue of integrin function through an R-Ras dependent pathway.
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3 integrin function. PEA-15 is a member of the death effector domain (DED)-containing family of molecules, which were previously only known to function in apoptosis. PEA-15 mediates its rescue of integrin function through an R-Ras dependent pathway.
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3 activation is probably due to a conformational change of the integrin.
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The contribution of the three hypothesized integrin-binding sites in fibrinogen to platelet-mediated clot retraction
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3 dependent process. These results suggest the presence in fibrin of an unknown platelet binding site that mediates clot retraction.
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3 dependent process. These results suggest the presence in fibrin of an unknown platelet binding site that mediates clot retraction.
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Identification of an interaction between the M-band protein skelemin and β-integrin subunits. Colocalization of a skelemin-like protein with β1- And β3-integrins in non-muscle cells
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3 integrin cytoplasmic binding protein. Although the functional significance of this association in platelets is unknown, it might play a role in cell spreading.
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3 integrin cytoplasmic binding protein. Although the functional significance of this association in platelets is unknown, it might play a role in cell spreading.
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Identification of a novel integrin signaling pathway involving the kinase Syk and the guanine nucleotide exchange factor Vav1
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A unique outside-in signaling pathway is described, which is downstream of Syk and Vav and involves a number of kinases such as JNK, Erk2 and PKB, as well as the adapter protein, Cbl. The potential functional significance of these events in platelets is currently unknown.
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Miranti CK, Leng L, Maschberger P, Brugge JS, Shattil SJ Identification of a novel integrin signaling pathway involving the kinase Syk and the guanine nucleotide exchange factor Vav1. Curr Biol. 8:1998;1289-1299. A unique outside-in signaling pathway is described, which is downstream of Syk and Vav and involves a number of kinases such as JNK, Erk2 and PKB, as well as the adapter protein, Cbl. The potential functional significance of these events in platelets is currently unknown.
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Miranti, C.K.1
Leng, L.2
Maschberger, P.3
Brugge, J.S.4
Shattil, S.J.5
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