Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression?

Biochem Soc Trans. 2002 Nov;30(Pt 6):959-63. doi: 10.1042/bst0300959.

Abstract

The phenotype of mitogen-activated protein kinase-activated protein kinase-2 (MK2) knockout mice revealed the essential role of this enzyme in post-transcriptional regulation of lipopolysaccharide-induced expression of cytokines such as tumour necrosis factor (TNF)-alpha, interleukin-6 and interferon-gamma, at the level of mRNA stability and translation. In the case of TNF-alpha, this regulation depends on the AU-rich element in TNF-alpha mRNA. In addition to cytokine expression, MK2 is also essential for cell migration in vitro. Although the role of MK2 in cytokine expression depends mainly on catalytic activity, its role in cell migration is also dependent on a proline-rich N-terminal motif. However, the molecular mechanisms involved and the relevant protein targets for MK2 are not completely defined. Here we discuss the possible mechanisms by which two potential target proteins of MK2, small heat-shock protein 25/27 (Hsp25/27) and tristetraprolin, could contribute to our understanding of the above regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins*
  • Gene Expression Regulation*
  • Heat-Shock Proteins*
  • Immediate-Early Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / physiology*
  • Models, Biological
  • Molecular Chaperones
  • Neoplasm Proteins / metabolism
  • Phenotype
  • Protein Biosynthesis
  • Protein Kinases*
  • Protein Serine-Threonine Kinases
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism
  • Tristetraprolin
  • p38 Mitogen-Activated Protein Kinases

Substances

  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • Hsbp1 protein, mouse
  • Immediate-Early Proteins
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • RNA, Messenger
  • Tristetraprolin
  • Zfp36 protein, mouse
  • Protein Kinases
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases