IL-4R(alpha), a new member that associates with Syk kinase: implication in IL-4-induced human neutrophil functions.
Although Syk has been reported to be associated with IL-2R beta [corrected] and IL-15R alpha in some hematopoietic cells, its association has never been investigated in the IL-4/IL-4R system. In this study, we demonstrate for the first time that Syk is constitutively associated with IL-4R(alpha)in human polymorphonuclear neutrophils (PMNs) and that IL-4 stimulation increases the amount of Syk associated with IL-4R(alpha). Moreover, upon IL-4 treatment, a pool of Syk associated with IL-4R(alpha) is phosphorylated. We also report that such association is not unique to PMNs because Syk associates with IL-4R(alpha) in Raji and in PBMC cells. Stimulation of PMNs by IL-4 increased the amount of Syk associated with PLC-gamma2, pAkt, and alpha-tubulin. Pretreatment of cells with the Syk-selective inhibitor piceatannol or Syk inhibitor II, significantly inhibited the ability of IL-4 to enhance phagocytosis and cell adhesion and to delay apoptosis, and these results correlate with the ability of piceatannol to reduce Syk activation and its association with IL-4R(alpha). Down-regulation of Syk by antisense techniques demonstrates the importance of Syk in the antiapoptotic effect of IL-4. We conclude that association of Syk to IL-4R(alpha) is of biological significance and that IL-4R(alpha) is a new candidate to be added to the few cytokine receptor components which associate with Syk.
Ennaciri
Jamila
J
Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, Institut national de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada.
Girard
Denis
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D053662:Interleukin-4 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D051966:Phospholipase C gamma / Q000276:immunology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D014404:Tubulin / Q000276:immunology / Q000378:metabolism; D000077191:Wortmannin
D000276:Adjuvants, Immunologic; D000730:Androstadienes; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; D014404:Tubulin; D015847:Interleukin-4; C041525:3,3',4,5'-tetrahydroxystilbene; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma; D000077191:Wortmannin