Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Pharmacol. 2010 Dec 15;80(12):1915-20. doi: 10.1016/j.bcp.2010.06.021. Epub 2010 Jun 23.

MAPKAP kinases MK2 and MK3 in inflammation: complex regulation of TNF biosynthesis via expression and phosphorylation of tristetraprolin.

Author information

  • 1Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.


Downstream of mitogen-activated protein kinases (MAPKs), three structurally related MAPK-activated protein kinases (MAPKAPKs or MKs) - MK2, MK3 and MK5 - signal to diverse cellular targets. Although there is no known common function for all three MKs, MK2 and MK3 are mainly involved in regulation of gene expression at the post-transcriptional level and are implicated in inflammation and cancer. MK2 and MK3 are phosphorylated and activated by p38(MAPKα,β) and, in turn phosphorylate various substrates involved in diverse cellular processes. In addition to forwarding of the p38-signal by MK2/3, protein complex formation between MK2/3 and p38 mutually stabilizes these enzymes and affects p38(MAPK) signaling in general. Among the substrates of MK2/3, there are mRNA-AU-rich-element (ARE)-binding proteins, such as tristetraprolin (TTP) and hnRNP A0, which regulate mRNA stability and translation in a phosphorylation-dependent manner. Phosphorylation by MK2 stabilizes TTP, releases ARE-containing mRNAs, such as TNF-mRNA, from default translational repression and inhibits their nucleolytic degradation. Here we demonstrate that MK2/3 also contribute to the de novo synthesis of TTP. Whether this contribution proceeds via transcription factors directly targeted by MK2/3 or via chromatin remodeling by the reported binding of MK2/3 to the polycomb repressive complex is still open. A model is proposed, which demonstrates how this new function of transcriptional activation of TTP by MK2/3 cooperates with the role of MK2/3 in post-transcriptional gene expression to limit the inflammatory response.

Copyright © 2010 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk