Atypical mitogen-activated protein kinases: structure, regulation and functions

Mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that play a central role in transducing extracellular cues into a variety of intracellular responses ranging from lineage specification to cell division and adaptation. Fourteen MAP kinase genes have been identified in the human genome, which define 7 distinct MAP kinase signaling pathways. MAP kinases can be classified into conventional or atypical enzymes, based on their ability to get phosphorylated and activated by members of the MAP kinase kinase (MAPKK)/MEK family. Conventional MAP kinases comprise ERK1/ERK2, p38s, JNKs, and ERK5, which are all substrates of MAPKKs. Atypical MAP kinases include ERK3/ERK4, NLK and ERK7. Much less is known about the regulation, substrate specificity and physiological functions of atypical MAP kinases.