Abstract
PI3Ks produce 3'-phosphoinositides (3'-PIs) including PI(3,4,5)P3 and PI(3,4)P2, whereas PTEN dephosphorylates 3'-PIs to decrease the contents of PI(3,4,5)P3 and PI(3,4)P2. Elevation of PI(3,4,5)P3 and PI(3,4)P2 contents induces activation of PDK1 and Akt, resulting in cell migration and cell survival. Very recently, it has been shown that Rho-ROCK stimulates PTEN, resulting in inhibition of Akt and cell migration. These observations led us to investigate the effects of Rho-stimulating GPCR agonist LPA on Akt activation and cell migration. In CHO cells that endogenously express LPA1 receptor, IGF-I stimulated Akt phosphorylation (P-Akt) and chemotaxis in a PI3K inhibitor-sensitive manner. In PTX-treaed cells, LPA inhibited IGF-I-induced P-Akt and chemotaxis. Y-27632, a ROCK inhibitor, prevented LPA-inhibition of IGF-I-induced P-Akt, indicating the ROCK mediates inhibition of P-Akt. However, Y-27632 failed to abrogate LPA-inhibition of IGF-I-induced chemotaxis. Thus, there was a discrepancy between LPA-induced inhibition of the cellular 3'-PIs amount, which is reflected by the extent of P-Akt, and inhibition of cell migration. These results suggest that LPA-induced inhibition of cell migration is not dependent on ROCK-mediated stimulation of PTEN and, thereby, reductions of cellular 3'-PIs contents [J Physiol Sci. 2006;56 Suppl:S119]
