MAPK Family

MAPK Family refers collectively to the mitogen-activated protein kinases, the evolutionarily conserved serine/threonine kinases ERK1/2, JNK1-3, p38α-δ and ERK5. Each module follows a three-tier architecture in which a MAPKKK phosphorylates a MAPKK, which doubly phosphorylates the terminal MAPK at a conserved TXY motif. ERK signaling supports proliferation and differentiation downstream of RAS, whereas JNK and p38 transduce stress, inflammatory and apoptotic cues. Because pathway hyperactivation drives many cancers and inflammatory diseases, the family has yielded numerous inhibitors, including MEK inhibitors in clinical oncology use.