Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression?. (November 2002)

• Record Type: Journal Article
• Authors: Kotlyarov, A.; Gaestel, M.
• Is Part Of: Biochemical Society transactions. Volume 30:Number 6(2002)
• Page Start: 959
• Page End: 963
• Publication Date: 2002-11
• Subjects: cell migration -- cytokine -- mouse knockout -- protein phosphorylation -- tumour necrosis factor; ARE, AU-rich element -- CHOP, cAMP response element-binding protein-homologous protein: Hsp, heat-shock protein -- IL, interleukin -- LPS, lipopolysaccharide -- MAPK, mitogen-activated protein kinase -- MK2, mitogen-activated protein kinase-activated protein kinase-2 -- NLS, nuclear localization signal -- PRM, proline-rich motif -- TIA-1, T-cell-restricted intracellular antigen-1 -- TIAR, TIA-1 related protein -- TNF, tumour necrosis factor -- TTP, tristetraprolin -- VASP, vasodilator-stimulated phosphoprotein; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0300959
• Languages: English
• ISSNs: 0300-5127

Abstract

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)-α, interleukin-6 and interferon-γ, at the level of mRNA stability and translation. In the case of TNF-α, this regulation depends on the AU-rich element in TNF-α 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.