Mitogen-activated protein kinase (MAPK) signaling pathways involve two closely related MAP kinases, known as extracellular-signal-related kinase 1 (ERK 1, p44) and 2 (ERK 2, p42). Growth factors, steroid hormones, G protein-coupled receptor ligands, and neurotransmitters can initiate MAPK signaling pathways. 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. The human ERK2 gene maps to chromosome 22q11.21 and encodes a 360-amino acid protein.