title: The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases.
abstract: Twenty years ago, the first description of a tristetraprolin (TTP) knockout mouse highlighted the fundamental role of TTP in the restraint of inflammation. Since then, work from several groups has generated a detailed picture of the expression and function of TTP. It is a sequence-specific RNA-binding protein that orchestrates the deadenylation and degradation of several mRNAs encoding inflammatory mediators. It is very extensively post-translationally modified, with more than 30 phosphorylations that are supported by at least two independent lines of evidence. The phosphorylation of two particular residues, serines 52 and 178 of mouse TTP (serines 60 and 186 of the human orthologue), has profound effects on the expression, function and localisation of TTP. Here, we discuss the control of TTP biology via its phosphorylation and dephosphorylation, with a particular focus on recent advances and on questions that remain unanswered.
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Clark
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, U.K.
authors.forename: Jonathan L E
authors.initials: JL
authors.lastname: Dean
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051816:Tristetraprolin; D012694:Serine; D010744:Phosphoric Monoester Hydrolases
keywords: MAPK p38; PP2A; dual-specificity phosphatases; mRNA stability; tristetraprolin