Simian virus 40 large tumor antigen modulates the Raf signaling pathway

The large tumor antigen of simian virus 40 (SVLT) is a potent oncogene. Alt hough inactivation of the p53 and pRb tumor suppressors has been causally l inked to the transforming properties of SVLT, its exact mechanism of action remains undefined. Previous data indicated that Ras is activated in SVLT-e xpressing cells. In this report we show that SVLT also increases Raf kinase activity in both insect and mammalian cells, thus identifying the Raf kina se as an additional target of SVLT. Our results further show that SVLT was still able to activate Raf in cells where Ras levels had been drastically r educed through expression of an antisense construct, indicating that SVLT m ay activate Raf at least partly by a mechanism that is independent of its s timulatory effect on Ras.