The flow of information from the cell surface to the nucleus often involves signaling cascades that include the small GTP-binding protein Ras. The retinoblastoma protein Rb is a downstream nuclear target of Ras activation and both proteins are implicated in regulating cell proliferation and differentiation. Lee et al. show that Rb may also signal back upstream to Ras. Cells lacking Rb had an increase in activated Ras during the G1 phase of the cell cycle. Ras activation occurred at the level of GTP binding. During the G1 phase, activation of Ras, in the absence of Rb, also required protein synthesis. Rb deficiency also resulted in a failure of cells to differentiate, but this was not linked to the ability of Rb to regulate transcription. The authors propose that Rb might control the activity of Ras by regulating the expression of a factor that affects GTP loading of Ras. This regulation may be linked to the influence of Rb on differentiation.
Lee, K.W., Ladha, M.H., McMahon, C., and Ewen, M.E. (1999) The retinoblastoma protein is linked to the activation of ras. Mol. Cell. Biol. 19: 7724-7732. [Online Journal]