Disease relevance of Trp-sfllrnp

• Most of the receptor-activated GTPase, stimulated by both thrombin and SFLLRNP in platelet membranes, was inhibited by prior treatment with pertussis toxin or N-ethylmaleimide, suggesting that under these conditions much of the thrombin receptor-stimulated GTPase in platelet membranes is a member of the pertussis toxin-sensitive G alpha i family [1].

High impact information on Trp-sfllrnp

• Treatment of quiescent rat aortic smooth muscle cells with either alpha-thrombin or a thrombin receptor-derived agonist peptide (SFLLRNP) resulted in pronounced increases in [3H]thymidine incorporation that were concentration dependent and reached a maximum of approximately 15-fold above serum-starved controls [2].
• In signal transduction studies, both thrombin and SFLLRNP treatment led to rapid tyrosine phosphorylation of proteins with apparent molecular masses of 42, 44, 75, 120, and 190 kD, respectively, as assessed by antiphosphotyrosine immunoblotting [2].
• Furthermore, in the Swiss 3T3 cells, simple addition of either alpha-thrombin or SFLLRNP failed to elicit a significant mitogenic response [2].
• Thrombin and SFLLRNP, but not phenylephrine, also increased membrane-associated Rho in intact RASMCs, consistent with selective activation of Rho by thrombin [3].
• Treatment of the cultures with a synthetic thrombin receptor-activating peptide (SFLLRNP) mimicked the deleterious effects of thrombin on motoneurons [4].

Biological context of Trp-sfllrnp

• In the absence of added growth factors, SFLLRNP fully mimicked the effects of thrombin at half-maximal concentrations of 30 microM for an increase in cell number and DNA synthesis and 100 nM for the reversal of stellation [5].
• 1. We studied the structure-activity profiles of four thrombin receptor-derived polypeptides (TRPs) (P5, SFLLR; P5-NH2, SFLLR-NH2; P7, SFLLRNP; P7-NH2, SFLLRN) in contractile human placental artery (PA), umbilical artery (UA) and umbilical vein (UV) preparations and in a human platelet aggregation assay [6].

Anatomical context of Trp-sfllrnp

• In contrast, the membranes prepared from CHRF-288 cells showed similar maximal SFLLRNP- and alpha-thrombin-stimulated GTPase activity [1].
• Here, we show that treatment with a synthetic SFLLRNP peptide induced a dose-dependent degeneration and death of spinal motoneurons both in highly enriched cultures and in the developing chick embryo in vivo [7].
• Northern analysis with authentic annexin V cDNA confirms that TP508, but not SFLLRNP, induces expression of annexin V in human fibroblasts [8].
• To test whether they might be mediated by different receptors, we examined the contribution of the G protein-coupled thrombin receptor to these responses in purified rat astrocytes by using the agonist peptide SFLLRNP [5].
• 3 The response to PAR1-AP (SFLLRNP) was significantly (P<0.05) reduced by the preceding stimulation with thrombin and PAR1-AP in the valvular endothelial cells, while, importantly, it remained unaffected by the preceding stimulation with either trypsin or PAR2-AP (SLIGRL) [9].

Associations of Trp-sfllrnp with other chemical compounds

• In contrast, 1 microM herbimycin fully inhibited the ability of thrombin and SFLLRNP to increase cell number and stimulate DNA synthesis [5].
• The subpopulation of stored PRP samples that were inactive with U46619-plus-epinephrine did not correspond to the subpopulation of samples that were nonresponsive to SFLLRNP, indicating that loss of activity with selected samples was possibly receptor specific [10].
• Platelet function was evaluated as aggregation induced by the synergistic agonist pair, U46619 (TXA2 mimetic) plus epinephrine or the strong agonists SFLLRNP (a peptide thrombin receptor agonist) or thrombin each added alone [10].
• However, the contractile response to thrombin and PAR1/PAR2-AP, SFLLRNP was not enhanced either by progesterone or 17beta-estradiol [11].
• Thrombin receptor-derived peptide SFLLRNP (one-letter amino acid code) which corresponds to the N-terminal heptapeptide of tethered ligand is able to activate thrombin receptor and to stimulate the phosphoinositide (PI) turnover [12].

Gene context of Trp-sfllrnp

• Thrombin and the 7-mer agonist peptide from its receptor (SFLLRNP) were compared for their ability to promote the binding of vWF to platelets [13].
• In contrast, treatment with the thrombin-tethered ligand receptor peptide TRP-7 (SFLLRNP) induced IL-6 production, but at lower levels than that induced by native alpha-thrombin [14].

References