Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression?
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.
Kotlyarov
A
A
Medical School Hannover, Institute of Biochemistry, Carl-Neuberg-Strasse 1, Germany.
Gaestel
M
M
D000818:Animals; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins; D017874:Immediate-Early Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D014176:Protein Biosynthesis; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D051816:Tristetraprolin; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D051816:Tristetraprolin; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C486113:Hsbp1 protein, mouse; C497553:Zfp36 protein, mouse