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United States Department of Agriculture

Agricultural Research Service

Title: Phosphorylation site analysis of the anti-inflammatory and mRNA-destabilizing protein tristetraprolin

Authors
item Cao, Heping
item Deterding, Lessa - USDHHS-NIH-NIEHS NC
item Blackshear, Perry - USDHHS-NIH-NIEHS NC

Submitted to: Expert Review of Proteomics
Publication Type: Review Article
Publication Acceptance Date: November 20, 2007
Publication Date: December 1, 2007
Citation: Cao, H., Deterding, L., Blackshear, P. 2007. Phosphorylation site analysis of the anti-inflammatory and mRNA-destabilizing protein tristetraprolin. Expert Review of Proteomics. 4(6):711-726.

Technical Abstract: Tristetraprolin (TTP/TIS11/ZFP36) is a member of the CCCH zinc finger proteins, and is an anti-inflammatory protein. Mice deficient in TTP develop a profound inflammatory syndrome with erosive arthritis, autoimmunity, and myeloid hyperplasia. TTP binds to AU-rich elements with high affinity for UUAUUUAUU nucleotides within mRNA sequences and causes destabilization of those mRNA molecules. TTP is phosphorylated extensively in vivo, and is a substrate for multiple protein kinases in vitro. A number of approaches have been used to identify its phosphorylation sites. This article highlights the recent progress and different approaches utilized for the identification of phosphorylation sites in mammalian TTP. Important, but limited, results are obtained using traditional methods including in vivo labeling, site-directed mutagenesis, phosphopeptide mapping, and protein sequencing. Mass spectrometry including MALDI/MS, MALDI/MS/MS, LC/MS/MS, IMAC/MALDI/MS/MS, and multidimensional protein identification technology has led the way in identifying TTP phosphorylation sites. The combination of these approaches has identified multiple phosphorylation sites in mammalian TTP, some of which are predicted by motif scanning to be phosphorylated by several protein kinases. This information should provide the molecular basis for future investigation of TTP’s regulatory functions in controlling pro-inflammatory cytokines.

Last Modified: 7/30/2014
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