| Research Abstract |
Phospholipase D has been known to be important signaling enzyme to regulate cell proliferation and survival. Two types of PLD(1,2) have been cloned in mammalian tissues and cells. The PLD1 and PLD2 are differently regulated and distributed in the cells. Sphingosine 1-phosphate(S1P) stimulation of S1P_3-overexpressing CHO cells induced activation of PLD, PI3-kinase, and Akt. S1P-induced activation of PI3-kinase and Akt was abrogated by 1-butanol, which inhibited phosphatidic acid(PA) formation by PLD. Overexpression of the wild-type PLD1,2 resulted in increased activation of Akt, ERK and p70S6 kinase in response to S1P. Actinomycine D(AchD) induced apoptosis in CHO cells, and the apoptosis was prevented by overexpression of PLD1,2. The treatment of CHO cells with AchD induced activation of survival signaling(PI3K, Akt, ERK, p70S6K) at earlier times of apoptosis. The activities of survival signaling were increased by overexpression of PLD1,2. These results demonstrate that PLD participates in the potentiation of survival signaling activation. We have found that PLD1 play a role in melanogenesis of mouse B16 melanoma cells. It has been shown that PLD1 negatively regulated the melanogenic signaling by modulating the expression of tyrosinase in B16 melanoma cells.
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