Thrombin receptor agonist peptide

All interactions between UFH and platelets are complex and only partially elucidated, but it is known that heparin itself stimulates platelets via a platelet-binding domain of heparin (14). In the therapeutic range, UFH induces the release of P-selectin and activates GPIIb/llla receptors when adenosine diphosphate (ADP) or thrombin receptor agonist peptide stimulates platelet responsibility, and then enhances platelet aggregation (15,16). Even in healthy individuals, agonist-induced platelet aggregation is often enhanced when heparin is added. 

Xiao Z, Theroux R Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol 2004 43 1 982-1988. 

Lau L-F, PumigliaK, Cote YP, Feinstein MB Thrombin-receptor agonist peptides, in contrast to thrombin itsdf, are not fiill agonists for activation and signal transduction in human platdets in the absence of platdd-derived secondary mediators. Biochem J 303 391,1994... 

Kramer RM, Roberts EF, Hydop PA, Utteriiack BG, Hui KY, Jakubowski JA Differential activation of thrombin receptor agonist peptide in human platdets. J Biol Chem 270 14816,1995... 

Kramer RM, Roberts EF,Hyslop PA UtterbackBG,HuiKY, and Jakubowski JA (1995). Differendal activation of cytosolic diospholipase A2 (cPLA2) by thrombin and thrombin receptor agonist peptide in human platelets. Evidence for activation of cPLA2 indepoident of the mitOgen-activated protein kinases ERKl/2. J. Biol. Chem. 270,14816-4823. 

FIGURE 30.4 The scheme of Thrombin Receptor Agonist Peptide (TRAP-6) encapsulation in PLGA microparticles by double (W1/0/W2) emulsion-evaporation technique. 

Stashevskaya, K., Grandfils, Ch., Markvicheva, E., and Strukova, S., In vitro study of Thrombin Receptor Agonist Peptide release from PLGA microbeads, in Proceedings of the XII International Workshop on Bioencapsulation, Victoria, Spain, September 24-26, 2004, 295-298. 

TRAPg Thrombin receptor agonist peptide 6, which contains residues 42—47 of the thrombin receptor... 

Jenkins AL, Bootman MD, Derridge MJ, Stone SR Differences in intracellolar calcium signaling after activation of the thrombin receptor by thrombin and agonist peptide in osteoUast-like cdls. J Biol Chem 269 17104,1994... 

McLaughlin, J. N., Shen, L., Holinstat, M., Brooks, J. D., Dibenedetto, E., and Hamm, H. E. (2005). Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. / Biol. Chem. 280, 25048-25059. 

At this point, we had assembled a preliminary model of the human thrombin receptor that contained all three extracellular loops linked to the seven TM domains, as well as the N-terminus out to residue 75. Docking studies with agonist peptide SFLLRN, and additional mutagenesis experiments, were carried out in parallel. Measurement of the effects of site-specific mutations in human PAR-1 identified several key amino acids of the receptor as being important for activation (Table 1),... 

Figure 9. Hydrophobic cluster involving Phe-182 (magenta), Leu-340 (orange), Tyr-337 (red), and Phe-339 (magenta) of the human thrombin receptor complexed with the Phe residue (white) of the agonist peptide.

Overall, our results provide a working hypothesis for the molecular recognition that occurs between the human thrombin receptor (PAR-1) and its agonist peptide SFLLRN. Similar features may contribute to the interactions of the X. laevis homologue of PAR-1 with TFRIFD and of human PAR-2 with SLIGKV, although... 

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