MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?
Synthetic glucocorticoids (GCs) potently inhibit the expression of pro-inflammatory genes and are widely used in the treatment of inflammatory diseases. However, some patients are resistant to the therapeutic effects of GCs, and many suffer deleterious side effects from these drugs. Furthermore, the precise mechanisms by which GCs inhibit pro-inflammatory gene expression remain unclear. A number of recent papers report that GCs induce the sustained expression of MAP kinase (MAPK) phosphatase 1 (MKP-1), a negative regulator of MAPK signal transduction pathways. The potential relevance of MKP-1 to some of the biological effects of GCs is discussed.
Clark
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AR
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom. andy.clarck@ic.ac.uk
D018797:Cell Cycle Proteins; D004351:Drug Resistance; D054638:Dual Specificity Phosphatase 1; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000201:enzymology; D017874:Immediate-Early Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018448:Models, Immunological; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases