抄録
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many of these responses are mediated by S1P receptors, S1P1/EDG1, S1P3/EDG3, and S1P2/EDG5. We previously showed that S1P2/EDG5, via G12 and G13 proteins, mediated inhibiton of insulin-like growth factor-I (IGF-I)-induced Rac activation and cell migration, whereas S1P1/EDG1 and S1P3/EDG3 each alone, via Gi protein, mediated Rac activation and stimulation of cell migration. However, it is not known how G12and G13 proteins mediate inhibition of Rac and cell migration in S1P2/EDG5 signaling. We found that the pretreatment with C3 toxin, which inactivates Rho, and the expresson of dominat negative Rho A prevented S1P2/EDG5-mediated inhibition of Rac and cell migration. On other hand, the expression of constitutively active Rho inhibited IGF-I induced Rac activation and cell migration. However, Rho kinase inhibitors did not affect S1P2/EDG5-mediated inhibition of Rac or cell migration. These results indicate that Rho, but not Rho kinase, mediates inhibition of Rac activity and cell mobility on stimulation of S1P2/EDG5. [Jpn J Physiol 54 Suppl:S77 (2004)]
