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: 8.56). 06/2007; 26(22):3240-53. DOI: 10.1038/sj.onc.1210415
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to investigate the mechanism of human esophageal Eca109 cells induced by Diosgenin (Dio), the p38 specific inhibitor SB203580 was used to inhibit the expression of p38 and Western blot was employed to detect the effect of SB203580 in Eca109 cells. MTT experiments were executed to detect the proliferation of the cells. Western blot was also applied to find the expression of phosphorylated p38 (p-p38). It is found that SB203580 can inhibit the expression of p38 in human esophageal cell Eca109. After treated with 50 μg/mL of Dio and 10 μg/mL of SB203580, the proliferation of cells showed significantly increase and the apoptosis of cells showed significantly decrease compared with the proliferation in the cells treated with Dio only. Moreover, p-p38 protein level was significantly decreased after treated by the two drugs. It is concluded that Dio may regulate esophageal Eca109 cells through p-p38 pathway.
    International Journal of Clinical and Experimental Medicine 01/2015; 8(2):2476-9. · 1.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analysing the origin and evolution of the ubiquitin signalling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole ubiquitin, SUMO and Ufm1 signalling networks by analysing representatives from all major eukaryotic, bacterial and archaeal lineages. We found that the ubiquitin toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic ubiquitin toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the ubiquitin-related genes, including the SUMO and Ufm1 ubiquitin-like systems. Ubiquitin and SUMO signalling further expanded during eukaryotic evolution, especially labelling and de-labelling enzymes responsible for substrate selection. Additionally, we analysed protein domain architecture evolution and found that multicellular lineages have the most complex ubiquitin systems in terms of domain architectures. Together, we demonstrate that the ubiquitin system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex post-translational regulation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Molecular Biology and Evolution 11/2014; DOI:10.1093/molbev/msu334 · 14.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.
    PLoS ONE 12/2014; DOI:10.1371/journal.pone.0114837 · 3.53 Impact Factor


Available from
May 30, 2014