MAP kinases and the control of nuclear events

Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Oncogene (Impact Factor: 8.46). 06/2007; 26(22):3240-53. DOI: 10.1038/sj.onc.1210415
Source: PubMed


The mitogen-activated protein kinases (MAPKs) are a family of serine/threonine kinases that play an essential role in signal transduction by modulating gene transcription in the nucleus in response to changes in the cellular environment. They include the extracellular signal-regulated protein kinases (ERK1 and ERK2); c-Jun N-terminal kinases (JNK1, JNK2, JNK3); p38s (p38alpha, p38beta, p38gamma, p38delta) and ERK5. The molecular events in which MAPKs function can be separated in discrete and yet interrelated steps: activation of the MAPK by their upstream kinases, changes in the subcellular localization of MAPKs, and recognition, binding and phosphorylation of MAPK downstream targets. The resulting pattern of gene expression will ultimately depend on the integration of the combinatorial signals provided by the temporal activation of each group of MAPKs. This review will focus on how the specificity of signal transmission by MAPKs is achieved by scaffolding molecules and by the presence of structural motifs in MAPKs that are dynamically regulated by phosphorylation and protein-protein interactions. We discuss also how MAPKs recognize and phosphorylate their target nuclear proteins, including transcription factors, co-activators and repressors and chromatin-remodeling molecules, thereby affecting an intricate balance of nuclear regulatory molecules that ultimately control gene expression in response to environmental cues.

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Available from: Adrian Gustavo Turjanski
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    • " and a central signaling cascade that is essential for the host immune response ( Krachler et al . , 2011 ) . In mammals , there are at least four subfamilies of MAPKs , including the extracellular signal - regulated kinases ( ERKs ) , the c - Jun NH 2 - terminal kinases ( JNKs ) , the p38 isoforms ( p38s ) , and ERK5 ( Tanoue and Nishida , 2003 ; Turjanski et al . , 2007 ) . These kinases are organized as parallel cascades in which the activation of each component is regulated upstream and downstream by phosphorylation events ( Chang and Karin , 2001 ) . As in mouse TG cells , a large amount of phosphorylated MAPK family protein is detected in bovine TG cells . The localization of actin , its associated"
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    • "N-terminal kinase (JNK), and p38 [16]. Previous studies have demonstrated that H. pylori-induced activation of MAPK mediates IL-8 expression by increasing NF-í µí¼…B and AP-1 DNA-binding activities [17] [18]. "
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