The activation of signal transduction pathways by growth factors, hormones and neurotransmitters is mediated through two closely related MAP kinases, p44 and p42, designated extracellular-signal related kinase 1 (ERK 1) and ERK 2, respectively. ERK proteins are regulated by dual phosphorylation at specific tyrosine and Threonine sites mapping within a characteristic Thr- Glu-Tyr motif. Phosphorylation at both the Thr and Tyr residues is required for full enzymatic activation. In response to activation, MAP kinases phos-phorylate downstream components on Serine and Threonine. Upstream MAP kinase regulators include MAP kinase kinase (MEK), MEK kinase and Raf-1. The ERK family has three additional members: ERK 3, ERK 5 and ERK 6.