Protein phosphatases and the regulation of MAP kinase activity

A family of dual specificity (Thr/Tyr) MAP kinase phosphatases (MKPs) have been identified in mammalian cells. These enzymes are implicated in negative feedback control of MAP kinase activity. This idea is supported by genetic and biochemical evidence which implicates homologous enzymes in the regulation of MAP kinases in yeasts and Drosophila. However, recent work in yeasts has shown that, in addition to these dual specificity MKPs, 'classical' tyrosine-specific phosphatases are also involved in the regulated dephosphorylation of MAP kinases. A picture is emerging in which a complex interplay between upstream activators and multiple protein phosphatases is responsible for the regulation of MAP kinase activity. The activities, substrate specificities and subcellular localisation of these protein phosphatases are likely to be key determinants of the biological outcome of signalling through different MAP kinase pathways in mammalian cells and tissues.