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Thrombin signalling and protease-activated receptors
Roles for PARs are beginning to emerge in haemostasis and thrombosis, inflammation, and perhaps even blood vessel development.
Protease‐activated receptors in hemostasis, thrombosis and vascular biology
  • S. Coughlin
  • Biology
    Journal of thrombosis and haemostasis : JTH
  • 1 August 2005
Roles for PARs in blood vessel formation and other processes during embryonic development are emerging, and whether these reflect new roles for the coagulation cascade and/or PAR signaling to other proteases remains to be explored.
A dual thrombin receptor system for platelet activation
It is reported that thrombin responses in platelets from PAR3-deficient mice were markedly delayed and diminished but not absent, and the identification of a two-receptor system for platelet activation byThrombin has important implications for the development of antithrombotic therapies.
Protease-activated receptor 3 is a second thrombin receptor in humans
Cl cloning and characterization of a new human thrombin receptor, designated protease-activated receptor 3 (PAR3) is reported, which can mediate throm-bin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, making it a candidate for the sought-after second platelet throm bin receptor.
Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.
Observations suggest that PAR1 and PAR4 account for most, if not all, thrombin signaling in platelets and that antagonists that block these receptors might be useful antithrombotic agents.
Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate
Separate sources provide S1P to plasma and lymph to help lymphocytes exit the low-S1P environment of lymphoid organs, and disruption of compartmentalized S 1P signaling is a plausible mechanism by which S1p-receptor-1 agonists function as immunosuppressives.
PAR3 is a cofactor for PAR4 activation by thrombin
Identification of the mechanisms by which the coagulation protease thrombin activates platelets is critical for understanding haemostasis and thrombosis. Thrombin activates cells at least in part by
Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa.
The results suggest that PAR2, although not activatable by thrombin, may nonetheless function as a sensor for coagulation proteases and contribute to endothelial activation in the setting of injury and inflammation.
Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.
The identification of the MCP-1 receptor and cloning of two distinct isoforms provide powerful tools for understanding the specificity and signaling mechanisms of this important chemokine.