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 受体激活沉淀复合物 最终导致血小板聚集和细胞凋亡的信号传导事件 增殖 血小板聚集最有效的刺激物之一 是凝血丝氨酸蛋白酶，α-凝血酶。 α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细胞外结构域。 凝血酶受体因此通过裂解和随后的 暴露与受体本身相连的肽图， 避免了对高细胞外肽激素的需要， 浓度. 一旦被α-凝血酶激活， 受体-分子内栓系配体复合物对蛋白质的开关 激酶级联、Ca++内流和基因转录。 当前工作 阐述了受体信号传导的各个方面， 通过特异性位点的次级凝血酶裂解下调 在凝血酶胞外结构域内。 使用质谱法 为了鉴定由凝血酶裂解a 重组凝血酶胞外结构域（JR 78）。 洞察 这些凝血酶受体肽之间的分子相互作用， 凝血酶应该为开发抗血栓药物提供线索 剂.

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.