Transduction of extracellular signals that stimulate cell proliferation requires the small GTPase Ras. Precisely which Ras signalling pathways are involved remains obscure, however, given the numerous potential Ras effectors(e.g. Raf, PI3 kinase and phospholipase Cϵ) and doubts concerning the validity of the overexpression studies often used to define them. Chris Marshall and co-workers have now dissected mitogenic signalling through Ras by examining the requirement for ERK (part of the Ras-Raf-MEK-ERK MAP kinase cascade) signalling in cells lacking the tumour suppressor RB, using inhibitors of MEK to block ERK activation. Among their results is the observation that, unlike wild-type cells, RB-/- mouse embryonic fibroblasts do not require significant ERK activation for exit from G0 phase and entry into S phase (see p. 4607). Since RB-/- cells require Ras for exit from G0,this key finding indicates that although Ras/ERK signalling is required for the G1/S transition, an ERK-independent Ras...

You do not currently have access to this content.