Background
Mitogen-activated protein (MAP) kinase cascades are activated by various extracellular stimuli, including growth factors. The MEK kinases (also designated MAP kinase kinase kinases, MKKKs, MAP3Ks or MEKKs) phosphorylate and thereby activate the MEKs (also called MAP kinase kinases or MKKs), including ERK, JNK and p38. These activated MEKs in turn phosphorylate and activate the MAP kinases. The MEK kinases include Raf-1, Raf-B, Mos, MEK kinase-1, MEK kinase-2, MEK kinase-3, MEK kinase-4 and ASK 1 (MEK kinase-5). MEK kinase-1 activates the ERK and c-Jun NH2-terminal kinase (JNK) pathways by phosphorylation of MAP2K1 and MAP2K4, and also activates the central protein kinases of the NFκB pathway, CHUK and IKBKB.