Fig. (1) The mitogen activated protein [MAP] kinase signalling pathways. The MAPK pathways include three main families (extracellular regulating kinases, c-Jun N-terminal kinases, and p38) that form an integrating and amplifying cascade of 3 kinase tiers. JNKs are activated via the sequential activation of protein kinases that includes two dual-specificity MAP kinase kinases (MKK4 and MKK7) and multiple MAP kinase kinase kinases (MKKKs) such as ASK1, MEKK1-4, TAK1-3 or MLK1-3. The top level shows the MKKKs, the second tier shows the MKKs, and the third tier consists of the MAP kinases. Each pathway activates a variety of transcription factors that regulate genes involved with cell survival, proliferation, and inflammation. There is considerable overlap of the genes regulated by the individual MAPKs. Gadd45ß is shown as a negative regulatory mechanism that suppresses JNK by blocking MKK7. ASK, apoptosis signal regulating kinase; ATF, activating transcription factor; IL, interleukin; MAPKAP, MAPK activated protein; MEKK, MKK kinase; TAK, TGFβ associated kinase.