The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines, and research investigators consider it an important target in the diagnosis and treatment of cancer. Activation of ERK1 and ERK2 requires phosphorylation by upstream kinases such as MAP kinase kinase (MEK), MEK kinase and Raf-1. ERK1 and ERK2 phosphorylation can occur at specific tyrosine and threonine sites mapping within consensus motifs that include the Threonine-Glutamate-Tyrosine motif. ERK activation leads to dimerization with other ERKs and subsequent localization to the nucleus. Active ERK dimers phosphorylate serine and threonine residues on nuclear proteins and influence a host of responses that include proliferation, differentiation, transcription regulation and development.
