title: IMPDHII protein inhibits Toll-like receptor 2-mediated activation of NF-kappaB.
abstract: Toll-like receptor 2 (TLR2) plays an essential role in innate immunity by the recognition of a large variety of pathogen-associated molecular patterns. It induces its recruitment to lipid rafts induces the formation of a membranous activation cluster necessary to enhance, amplify, and control downstream signaling. However, the exact composition of the TLR2-mediated molecular complex is unknown. We performed a proteomic analysis in lipopeptide-stimulated THP1 and found IMPDHII protein rapidly recruited to lipid raft. Whereas IMPDHII is essential for lymphocyte proliferation, its biologic function within innate immune signal pathways has not been established yet. We report here that IMPDHII plays an important role in the negative regulation of TLR2 signaling by modulating PI3K activity. Indeed, IMPDHII increases the phosphatase activity of SHP1, which participates to the inactivation of PI3K.
authors: Paris Descartes University, 75006 Paris, France.
authors: Julie
authors: J
authors: Toubiana
authors: Anne-Lise
authors: AL
authors: Rossi
authors: David
authors: D
authors: Grimaldi
authors: Nadia
authors: N
authors: Belaidouni
authors: Philippe
authors: P
authors: Chafey
authors: Guilhem
authors: G
authors: Clary
authors: Emilie
authors: E
authors: Courtine
authors: Frederic
authors: F
authors: Pene
authors: Jean-Paul
authors: JP
authors: Mira
authors: Yann-Erick
authors: YE
authors: Claessens
authors: Jean-Daniel
authors: JD
authors: Chiche
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6