Biological functions of a lipid mediator, sphingosine 1-phosphate

1) Sphingosine 1 -phosphate （Sph- 1 -p）在血小板相关血管生物学中的作用。(A)通过RT-PCR分析，我们发现Edg2、4、6和7在人血小板中表达。(B)我们从人血小板中纯化了一种新的鞘氨醇激酶。(C)利用新的二维TPC分离系统，首次发现活化血小板可同时释放Sph-1-P和LPA。(D)我们发现活化血小板释放的Sph-1-P诱导体外血管生成和平滑肌细胞收缩。2)除了已知的鞘氨醇激酶（1和2）外，我们还鉴定并克隆了两个新的鞘氨醇激酶（3和4）。3)通过Edg-5激活Rho和FAK可以调节细胞运动。4) Sph-1-P受体的研究。(A)我们首先发现edg1和edg6在Asp残基上被n -糖基化，并提出糖基化在质膜上向微结构域的受体动力学中的作用。(B)我们通过计算机建模和突变体分析确定了Edg-6中的配体结合氨基酸残基。

1) Roles of Sphingosine 1 -phosphate (Sph- 1 -P) in Platelet-related blood vessel biology.(A) By RT-PCR analysis, we identified that Edg2, 4, 6, and 7 are expressed in human platelets. (B) We purified a novel sphingosine kinase from human platelets. (C) We found for the first time that both Sph-1-P and LPA are released from activated platelets by using new two dimensional TPC separation system. (D) We showed that Sph-1-P released from activated platelets induces in vitro angiogenesis and smooth muscle cell contraction.2) Besides so-far known sphingosine kinases (1 and 2), we identified and cloned two novel sphingosine kinases (3 and 4).3) Activation of Rho and FAK through Edg-5 was suggested to regulate cell motility.4) Studies on Sph-1-P receptors.(A) We first showed that Edg 1 and Edg 6 are N-glycosylated on Asp residue and suggested the roles of glycosylyation on the receptor dynamics toward microdomain in plasmamembrane. (B) We identified ligand- binding amino acid residues in Edg-6 from computer modeling and mutant analysis.