The Regulation of MAP Kinase Pathways by MAP Kinase Phosphatases

Mitogen activated protein (MAP) kinase signal transduction pathways are evolutionary conserved protein modules that play a central role in conveying information from the extracellular environment into cytoplasmic and nuclear responses (1,2) The modules consist of a three component kinase cascade (Fig. 1) (see Chapter 9). After its activation by an upstream component, a serine-threonine kinase (a MAP kinase kinase kinase or MEKK) phosphorylates and thereby activates a dual specificity kinase (MAP kinase kinase or MEK) which in turn phosphorylates a MAP kinase on threonine and tyrosine resulting in its activation. Dual phosphorylation of MAP kinase on the relevant threonine and tyrosine, a TXY motif in kinase subdomain VIII, is required because neither phosphorylation alone is sufficient for activity.