Article

Differential regulation and properties of MAPK

Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Oncogene (Impact Factor: 8.46). 06/2007; 26(22):3100-12. DOI: 10.1038/sj.onc.1210392
Source: PubMed

ABSTRACT

Mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs including embryogenesis, proliferation, differentiation and apoptosis based on cues derived from the cell surface and the metabolic state and environment of the cell. In mammals, there are more than a dozen MAPK genes. The best known are the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK(1-3)) and p38(alpha, beta, gamma and delta) families. ERK3, ERK5 and ERK7 are other MAPKs that have distinct regulation and functions. MAPK cascades consist of a core of three protein kinases. Despite the apparently simple architecture of this pathway, these enzymes are capable of responding to a bewildering number of stimuli to produce exquisitely specific cellular outcomes. These responses depend on the kinetics of their activation and inactivation, the subcellular localization of the kinases, the complexes in which they act, and the availability of substrates. Fine-tuning of cascade activity can occur through modulatory inputs to cascade component from the primary kinases to the scaffolding accessory proteins. Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity.

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    • "Mitogen-activated protein kinase (MAPK) kinase (MAP2K) kinases (MAP3Ks) are important regulators of IkB kinases (IKKs) and MAP2Ks (Dong et al., 2002; Ghosh and Karin, 2002; Kyriakis and Avruch, 2001; Raman et al., 2007; Suddason and Gallagher, 2015). Nineteen MAP3Ks are present in mammals, though their precise roles in regulating the immune system are not fully understood (Karin and Gallagher, 2005; Suddason and Gallagher, 2015). "
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