The versatile role of MSKs in transcriptional regulation

Trends Biochem Sci. 2009 Jun;34(6):311-8. doi: 10.1016/j.tibs.2009.02.007. Epub 2009 May 21.


Among the mitogen-activated protein kinase (MAPK) targets, MSKs (mitogen- and stress-activated protein kinases) comprise a particularly interesting protein family. Because MSKs can be activated by both extracellular-signal-regulated kinase and p38 MAPKs, they are activated by many physiological and pathological stimuli. About ten years after their original discovery, they have been recognized as versatile kinases regulating gene transcription at multiple levels. MSKs directly target transcription factors, such as cAMP-response-element-binding protein and nuclear factor-kappaB, thereby enhancing their transcriptional activity. They also induce histone phosphorylation, which is accompanied by chromatin relaxation and facilitated binding of additional regulatory proteins. Here, we review the current knowledge on MSK activation and its molecular targets, focusing on recent insights into the role of MSKs at multiple levels of transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • CREB-Binding Protein / metabolism
  • Cell Cycle Proteins
  • Cell Death
  • Chromatin / metabolism
  • Histones / chemistry
  • Humans
  • Inflammation
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / physiology*
  • Models, Biological
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic*


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Chromatin
  • EIF4EBP1 protein, human
  • Histones
  • Phosphoproteins
  • RELA protein, human
  • Transcription Factor RelA
  • CREB-Binding Protein
  • Mitogen-Activated Protein Kinase Kinases