NOVEL NEW ENZYME & PRODUCT FROM ENCYSTING GIARDIA

本研究的重点是7-跨膜/G-蛋白偶联 人凝血酶受体。受体激活沉淀复合体 信号事件最终导致血小板聚集和细胞 扩散。对血小板聚集最有效的刺激因素之一 是凝血的丝氨酸蛋白酶，即α-凝血酶。甲型凝血酶 通过识别和切割N-末端来发挥作用 位于血小板膜上的受体的胞外区。 因此，凝血酶受体被切割和随后的 暴露与受体本身捆绑的多肽Figand，这 消除了对高胞外肽激素的需求 集中精神。一旦被α-凝血酶激活， 蛋白质上的受体-分子内拴系配体复合体开关 激酶级联、钙离子内流和基因转录。当前工作 涉及受体信号的各个方面，包括受体 凝血酶在特定部位的二次裂解下调 在凝血酶胞外区内。使用了质谱学 鉴定凝血酶裂解产生的反应产物 重组凝血酶胞外区(JR78)。洞察 凝血酶受体多肽与凝血酶的分子相互作用 凝血酶应为抗血栓药物的发展提供先导 探员们。

This research focuses on the 7-transmembrane/G-protein coupled human thrombin receptor. Receptor activation precipitates complex signaling events culminating in platelet aggregation and cellular proliferation. One of the most potent stimuli of platelet aggregation is the blood clotting serine protease, alpha-thrombin. Alpha-thrombin exerts its action by recognizing andcleaving the N-terminal extracellular domain of a receptor located on the platelet membrane. Thethrombin receptor is thus activated by cleavage and subsequent exposure of a peptide figand tethered to the receptor itself, which obviates the need for high extracellular peptide hormone concentration. Once activated by alpha-thrombin, the receptor-intramolecular tethered ligand complex switches on a protein kinase cascade, Ca++ influx, and gene transcription. Current work addresses various aspects of receptor signaling including receptor down-regulation by secondary thrombin cleavage at specific sites within the thrombin extracellular domain. Mass spectrometry is used to identify reaction products generated by thrombin cleavage of a recombinant extracellular domain of thrombin (JR78). Insight into the molecular interactions between these thrombin receptor peptides and thrombin should provide leads for the development of anti-thrombotic agents.