Dual specificity kinases--a new family of signal transducers.

Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms through which cells modulate protein activity in response to environmental stimuli. The eukaryotic molecules which are responsible for the phosphorylation of serine, threonine and tyrosine residues appear to have co-ordinately evolved from simple prokaryotic enzymes which primarily respond to nutritional cues. In multicellular eukaryotes the complexity of data transfer greatly exceeds that of simple bacteria. The eukaryotic cell needs to exchange information with neighbouring and distant sister cells. Positional, nutritional and hormonal data are transmitted from the extracellular milieu across the plasma membrane and into the cytoplasm. In certain cases the signal must pass into the nucleus or other subcellular organelles where it is decoded and the proper cellular response initiated. All of these events have been shown to have a protein kinase component and it seems likely that in mammalian cells over 1,000 different kinase molecules have evolved to form the requisite signal transducing networks. In this review we describe a previously unappreciated family of protein kinases, the dual specificity or DSK kinases, which play important roles in the regulation of normal cellular growth and differentiation.