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The p38 MAPK signalling pathway plays an important role in inflammation and other physiological processes. Specific inhibitors of p38 alpha and beta MAPK block production of the major inflammatory cytokines (i.e. tumour necrosis factor-alpha and interleukin-1) and other proteins (e.g. cyclooxygenase-2), and are anti-inflammatory in animal models of disease. A major function of the pathway is post-transcriptional control of inflammatory gene expression. Many of the mRNAs are unstable (or untranslatable) because of AU-rich elements in the 3'untranslated region. Signalling in the p38 pathway counteracts these and stabilizes the mRNAs by preventing their otherwise rapid de-adenylation.

Original publication

DOI

10.1016/j.coph.2004.03.009

Type

Journal article

Journal

Current opinion in pharmacology

Publication Date

08/2004

Volume

4

Pages

372 - 377

Addresses

Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, 1 Aspenlea Road, London W6 8LH, UK. j.saklatvala@imperial.ac.uk

Keywords

Animals, Humans, Inflammation, Protein-Serine-Threonine Kinases, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Tumor Necrosis Factor-alpha, Intracellular Signaling Peptides and Proteins, Enzyme Inhibitors, Signal Transduction, Transcription, Genetic