ESSENTIAL ROLE FOR NUCLEAR PHOSPHOLIPASE-C BETA(1) IN INSULIN-LIKE-GROWTH-FACTOR I-INDUCED MITOGENESIS

The nucleus has been shown to be a site for the inositol lipid cycle t hat can be affected by treatment of quiescent cells with growth factor s such as insulin-like growth factor I (IGF-I), Indeed, the exposure o f Swiss 3T3 cells to IGF-I results in a rapid and transient increase i n nuclear phospholipase C (PLC) beta(1) activity, In addition, several other reports have shown the involvement of PLC beta(1) in nuclear si gnaling in different cell types, Although the demonstration of phospha tidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate hy drolysis by nuclear PLC beta(1) established the existence of nuclear P LC signaling, the significance of this autonomous pathway in the nucle us has yet to be thoroughly clarified, By inducing both the inhibition of PLC beta(1) expression by antisense RNA and its overexpression, we show that this nuclear PLC is essential for the onset of DNA synthesi s following IGF-I stimulation of quiescent Swiss 3T3 cells.