Differential regulation and properties of MAPKs

Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Oncogene (Impact Factor: 8.56). 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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    • "Indeed, several molecular pathways have been reported to be involved in the neurological damage caused by exposure to an electromagnetic field, such as the caspase3-dependent pathway (Liu et al., 2012), cAMP/PKA pathway (He et al., 2013), ATM-Chk2-p21 Pathway (Huang et al., 2014) and ERK pathway (Caraglia et al., 2005). Among these pathways, ERK1/2, a member of the mitogenactivated protein kinase (MAPK) family, plays a crucial role in signal transduction pathways related to cell growth, differentiation and albumin extravasations (Gorostizaga et al., 2013; Raman et al., 2007). The activity and expression of ERK1/2 is dependent on the phosphorylation process, which is modulated by MAP kinase phosphatase-1 (mkp-1) a short-lived nuclear enzyme (Gorostizaga et al., 2013). "
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    Brain Research 01/2015; 1601. DOI:10.1016/j.brainres.2015.01.019 · 2.83 Impact Factor
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    • "Differences in ERK activation have also been correlated with separation of the ab and gd T cell fates, although the importance of these differences in controlling the ab versus gd lineage separation process has never been investigated. Despite the central role that ERK signaling plays in essentially every lymphoid fate decision, the basis by which differences in ERK signaling promote the specification of alternative cell fates remains poorly understood (Raman et al., 2007). Consequently, we have investigated the basis by which differences in ERK signaling specify alternate developmental fates, using separation of the ab and gd lineages as a model. "
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    ABSTRACT: Gradations in extracellular regulated kinase (ERK) signaling have been implicated in essentially every developmental checkpoint or differentiation process encountered by lymphocytes. Yet, despite intensive effort, the molecular basis by which differences in ERK activation specify alternative cell fates remains poorly understood. We report here that differential ERK signaling controls lymphoid-fate specification through an alternative mode of action. While ERK phosphorylates most substrates, such as RSK, by targeting them through its D-domain, this well-studied mode of ERK action was dispensable for development of γδ T cells. Instead, development of γδ T cells was dependent upon an alternative mode of action mediated by the DEF-binding pocket (DBP) of ERK. This domain enabled ERK to bind a distinct and select set of proteins required for specification of the γδ fate. These data provide the first in vivo demonstration for the role of DBP-mediated interactions in orchestrating alternate ERK-dependent developmental outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.
    Immunity 12/2014; 41(6):934-946. DOI:10.1016/j.immuni.2014.10.021 · 19.75 Impact Factor
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    • "ROS activate the MAPK pathways , which are implicated in cellular survival and apoptosis ( Raman et al . , 2007 ) . The dynamic equilibrium between the opposing effects of anti - apoptotic ERK and pro - apoptotic p38 / JNK MAPK might be critical in determining whether cells survive or undergo apoptosis ( Fan et al . , 2007 ; Xia et al . , 1995 ) . In the present study , the phosphorylation of ERK in LAMP - treated PBMCs was increased a little at "
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