| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
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, S1P_1/EDG1, S1P_3/EDG3, and S1P_2/EDG5. We previously showed that S1P_2/EDG5, via G_<12> and G_<13> proteins, mediated inhibiton of insulin-like growth factor-I (IGF-I)-induced Rac activation and cell migration, whereas S1P_1/EDG1 and S1P_3/EDG3 each alone, via G_1 protein, mediated Rac activation and stimulation of cell migration. However, it is not known how G_<12> and G_<13> proteins mediate inhibition of Rac and cell migration in S1P_2/EDG5 signaling. We found that the pretreatment with C3 toxin, which inactivates Rho, and the expresson of dominat negative Rho A prevented S1P_2/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 S1P_2/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 S1P_2/EDG5.
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