Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-alpha, IL-1beta, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation (P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration (P < 0.00001) as well as mRNA expression of TNF-alpha, IL-8, and human beta-defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn's disease and correlated highly with the IL-8 expression in these lesions (r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and IEC migration.
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PMID:IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. 1653 74

Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines produced by activated T cells and is involved in several tissue responses. IL-22 signals through a heterodimeric receptor composed of IL-22 receptor 1 (IL-22R1) and IL-10R2, and the intracellular signaling pathways mediated by IL-22 receptor are not completely known. Here we investigate the effect of Src homology-2 containing protein-tyrosine phosphatase (Shp2) on IL-22 signaling pathway using SW480 colon cancer cells as a model. The results show that IL-22 induces IL-22R1 phosphorylation, and Shp2 is recruited to the tyrosine phosphorylated IL-22R1 upon IL-22 stimulation. Furthermore, Tyr251 and Tyr301 of IL-22R1 are required for Shp2 binding to the IL-22R1. Shp2 binding to IL-22R1 and Shp2 protein tyrosine phosphatase activity are required for activation of MAP kinases and signal transducer and activator of transcription (STAT3) phosphorylation by IL-22. These results reveal a critical role of Shp2 in IL-22 mediated signal transduction pathways.
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PMID:Association of Shp2 with phosphorylated IL-22R1 is required for interleukin-22-induced MAP kinase activation. 2067 Nov 17