P44/42 MAPK (Erk1 and Erk2), SAPK and p38 MAPK function in protein kinase cascades that play a critical role in the regulation of cell growth, and the differentiation and control of cellular responses to cytokines and stress. p44/42 MAPK (Erk1 and Erk2) is activated by growth and neurotrophic factors. Activation occurs through phosphorylation of threonine and tyrosine (202 and 204 of human MAP kinase [Erk1]) at the sequence T*EY* by a single upstream MAP kinase kinase (MEK). SAPK and p38 MAPK are activated by inflammatory cytokines and a wide variety of cellular stresses. Activation of SAPK occurs via phosphorylation at Thr183 and Tyr185 by the dual specificity enzyme SEK/MKK4. Both MKK3 and SEK phosphorylate p38 MAPK on tyrosine and threonine at the sequence T*GY* resulting in p38 activation.