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.
Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, Institut national de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada.
Jamila
J
Ennaciri
Denis
D
Girard
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