Biological functions of a lipid mediator, sphingosine 1-phosphate

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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.