It is taken for granted nowadays that extracellular signals are amplified and transduced inside cells by protein kinase cascades. Hundreds of different protein kinases have already been identified and the rate of discovery of new kinases shows no sign of slowing. Until recently, however, relatively little was known about how all these different protein kinases are orchestrated within signalling pathways. Recent biochemical and genetic studies from a variety of model systems have defined related cascades of sequentially activating protein kinases that link receptorassociated guanine nucleotide-binding proteins at the cell surface to the regulation of transcription facto’rs in the nucleus.