Targeting Syk as a treatment for allergic and autoimmune disorders

Bibliography

• TANIGUCHI T, KOBAYASHI T, KONDO J et al.: Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis. J. Biol. Chem. (1991) 266(24):15790–15796.
   PubMed Web of Science ®Google Scholar
• TURNER M, SCHWEIGHOFFER E, COLUCCI F, DI SANTO JP, TYBULEWICZ VL: Tyrosine kinase SYK: essential functions for immunoreceptor signalling. Immunol. Today (2000) 21(3):148–154. This review comprehensively describes the Syk-deficient =rine phenotypes and the role for Syk in haematopoietic cell functions.
   Google Scholar
• SADA K, TAKANO T, YANAGI S, YAMAMURA H: Structure and function of Syk protein-tyrosine kinase. Biochem. (Tokyo) (2001) 130(2):177–186.
   PubMed Web of Science ®Google Scholar
• KUROSAKI T: Regulation of B cell fates by BCR signaling components. Curt: Opin. Immunol (2002) 14(3):341–347.
   PubMed Web of Science ®Google Scholar
• ABTAHIAN F, GUERRIERO A, SEBZDA E et al.: Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science (2003) 299(5604):247–251.
   PubMed Web of Science ®Google Scholar
• ••This seminal paper demonstrates that thehaemorrhagic and lethal phenotypes observed in Sykl- mice are caused by a defect in vascular and lymphatic vessel development rather than an intrinsic platelet or endothelial cell defect.
   Google Scholar
• SIRAGANIAN RP, ZHANG J, SUZUKI K, SADA K: Protein tyrosine Expert Op/n. Investig. Drugs (2004) 13(7)755 kinase Syk in mast cell signaling. MM. Immunol (2002) 38(16–18):1229-1233.
   Google Scholar
• KESHVARA LM, ISAACSON CC, YANKEE TM et al.: Syk- and Lyn-dependent phosphorylation of Syk on multiple tyrosines following B cell activation includes a site that negatively regulates signaling. Immunol (1998) 161(10):5276–5283.
   Web of Science ®Google Scholar
• BALDOCK D, GRAHAM B, AKHLAQ M et al: Purification and characterization of human Syk produced using a baculovirus expression system. Protein Expr: Purif (2000) 18(1):86–94.
   PubMed Web of Science ®Google Scholar
• KUROSAKI T, JOHNSON SA, PAO L et al.: Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling. Exp. Med. (1995) 182(6):1815–1823.
   PubMed Web of Science ®Google Scholar
• ZHANG J, BILLINGSLEY ML, KINCAID RL, SIRAGANIAN RP: Phosphorylation of Syk activation loop tyrosines is essential for Syk function. An in vivo study using a specific anti-Syk activation loop phosphotyrosine antibody. Biol. Chem. (2000) 275(45):35442–35447.
   Google Scholar
• OTA S, HAZEKI K, RAO N et a/.: The RING finger domain of Cbl is essential for negative regulation of the Syk tyrosine kinase. Biol. Chem. (2000) 275(1):414–422.
   Google Scholar
• LUPHER ML, JR., RAO N, LILL NL et al.: Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323. Biol. Chem. (1998) 273(52):35273–35281.
   Google Scholar
• LUPHER ML, JR., REEDQUIST KA, MIYAKE S, LANGDON WY, BAND H: A novel phosphotyrosine-binding domain in the N-terminal transforming region of Cbl interacts directly and selectively with ZAP-70 in T cells. Biol. Chem. (1996) 271(39)24063–24068.
   Google Scholar
• YANKEE TM, KESHVARA LM, SAWASDIKOSOL S, HARRISON ML, GEAHLEN RL: Inhibition of signaling through the B cell antigen receptor by the protooncogene product, c-Cbl, requires Syk tyrosine 317 and the c-Cbl phosphotyrosine-binding domain. Immunol (1999) 163(11):5827–5835.
   Web of Science ®Google Scholar
• FUTTERER K, WONG J, GRUCZA RA, CHAN AC, WAKSMAN G: Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory 5H2 domains bound to a dually phosphorylated ITAM peptide. J. Ma Biol. (1998) 281(3):523–537.
   Web of Science ®Google Scholar
• DAERON M: Fc receptor biology. Ann. Rev Immunol (1997) 15:203–234.
   PubMed Web of Science ®Google Scholar
• RAVETCH JV, BOLLAND S: IgG Fc receptors. Ann. Rev Immunol (2001) 19:275–290.
   PubMed Web of Science ®Google Scholar
• RAVETCH JV: Fc Receptors. In: Fundamental Immunology Paul WE (Ed.), Lippincott, Williams and Wilkins, Philadelphia, PA, USA (2003): 685–700.
   Google Scholar
• •A comprehensive review of Fc receptor biology.
   Google Scholar
• LIN S, CICALA C, SCHARENBERG AM, KINET JP: The Fc (e) RIB subunit functions as an amplifier of Fc(E)RIy-mediated cell activation signals. Cell (1996) 85(7):985–995.
   PubMed Web of Science ®Google Scholar
• PAO LI, FAMIGLIETTI SJ, CAMBIER JC: Asymmetrical phosphorylation and function of immunoreceptor tyrosine-based activation motif tyrosines in B cell antigen receptor signal transduction. J. Immunol (1998) 160(7):3305–3314.
   PubMed Web of Science ®Google Scholar
• CAMBIER JC: Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM). Immunol (1995) 155(7):3281–3285.
   Google Scholar
• ROWLEY RB, BURKHARDT AL, CHAO HG, MATSUEDA GR, BOLEN JB: Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation.j Biol. Chem. (1995) 270(19):11590–11594.
   Google Scholar
• KRISHNAN S, WARKE VG, NAMBIAR MP, TSOKOS GC, FARBER DL: The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells. Immunol (2003) 170(8):4189–4195.
   Web of Science ®Google Scholar
• NADLER MJ, MATTHEWS SA, TURNER H, KINET JP: Signal transduction by the high-affinity immunoglobulin E receptor Fc epsilon RI: coupling form to function. Adv. Immunol (2000) 76:325–355.
   PubMed Web of Science ®Google Scholar
• RIVERA J: Molecular adapters in Fc(epsilon)RI signaling and the allergic response. Carr. Opin. Immunol (2002) 14(6):688–693.
   PubMed Web of Science ®Google Scholar
• •Describes the multiple players involved in FcERI signalling function and regulation.
   Google Scholar
• KAWAKAMI T, GALLI SJ: Regulation of mast-cell and basophil function and survival by IgE. Nat. Rev Immunol (2002) 2(10):773–786.
   PubMed Web of Science ®Google Scholar
• ••A review of FcERI signalling regulation anda comprehensive summary of the effects and implications by IgE on the survival of mast cell and basophils.
   Google Scholar
• SIRAGANIAN RP: Mast cell signal transduction from the high-affinity IgE receptor. Cuir. Opin. Immunol (2003) 15(6):639–646.
   PubMed Web of Science ®Google Scholar
• ••An up-to-date review of FcERI signalingregulation.
   Google Scholar
• JOUVIN MH, ADAMCZEWSKI M, NUMEROF R et al: Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. j. Biol. Chem. (1994) 269(8):5918–5925.
   PubMed Web of Science ®Google Scholar
• KIMURA T, KIHARA H, BHATTACHARYYA S et al.: Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor. Biol. Chem. (1996) 271(44):27962–27968.
   Web of Science ®Google Scholar
• SHIUE L, ZOLLER MJ, BRUGGE JS: Syk is activated by phosphotyrosine-containing peptides representing the tyrosine-based activation motifs of the high affinity receptor for IgE. J. Biol. Chem. (1995) 270(18):10498–10502.
   PubMed Web of Science ®Google Scholar
• SHIUE L, GREEN J, GREEN OM et al: Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI. Ma Cell. Biol. (1995) 15(1):272–281.
   Web of Science ®Google Scholar
• COSTELLO PS, TURNER M, WALTERS AE et al: Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells. Oncogene (1996) 13(12):2595–2605.
   PubMed Web of Science ®Google Scholar
• •Using Sykl- mast cells, this report demonstrates that Syk regulates the synthesis and release of the three major classes of allergic mediators (granule contents, lipid metabolites and cytokines) following FcERI stimulation.
   Google Scholar
• HENDRICKS-TAYLOR LR, MOTTO DG, ZHANG J, SIRAGANIAN RP, KORETZKY GA: SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells. J. Biol. Chem. (1997) 272(2):1363–1367.
   PubMed Web of Science ®Google Scholar
• TERAMOTO H, SALEM P, ROBBINS KC, BUSTELO XR, GUTKIND JS: Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Racl-JNK pathway. Biol. Chem. (1997) 272(16):10751–10755.
   Web of Science ®Google Scholar
• SAITOH S, ARUDCHANDRAN R, MANETZ TS et al: LAT is essential for Fc(epsilon)RI-mediated mast cell activation. Immunity (2000) 12(5):525–535.
   PubMed Web of Science ®Google Scholar
• MANETZ TS, GONZALEZ- ESPINOSA C, ARUDCHANDRAN R et al.: Vavl regulates phospholipase cgamma activation and calcium responses in mast cells. MM. Cell. Biol. (2001) 21(11):3763–3774.
   Web of Science ®Google Scholar
• KIMURA T, HISANO M, INOUE Y, ADACHI M: Tyrosine phosphorylation of the linker for activator of T cells in mast cells by stimulation with the high affinity IgE receptor. Immunol Lett. (2001) 75(2):123–129.
   PubMed Web of Science ®Google Scholar
• FITZER-ATTAS CJ, LOWRY M, CROWLEY MT et al.: Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn. J. Exp. Med. (2000) 191(4):669–682.
   PubMed Web of Science ®Google Scholar
• ZHANG W, IRVIN BJ, TRIBLE RP, ABRAHAM RT, SAMELSON LE: Functional analysis of LAT in TCR-mediated signaling pathways using a LAT-deficient Jurkat cell line. hat. Immunol (1999) 11(6):943–950.
   Web of Science ®Google Scholar
• ZHANG W, TRIBLE RP, ZHU M et al.: Association of Grb2, Gads, and phospholipase C71 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. J. Biol. Chem. (2000) 275(30):23355–23361.
   Google Scholar
• PASQUET JM, GROSS B, QUEK L et aL: LAT is required for tyrosine phosphorylation of phospholipase C72 and platelet activation by the collagen receptor GPVI. Ma Cell. Biol. (1999) 19(12):8326–8334.
   Web of Science ®Google Scholar
• ZHANG W, SLOAN-LANCASTER J, KITCHEN J, TRIBLE RP, SAMELSON LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell (1998) 92(1):83–92.
   PubMed Web of Science ®Google Scholar
• WU J, MOTTO DG, KORETZKY GA, WEISS A: Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity (1996) 4(6):593–602.
   PubMed Web of Science ®Google Scholar
• JORDAN MS, SINGER AL, KORETZKY GA: Adaptors as central mediators of signal transduction in immune cells. Nat. Immunol (2003) 4(2):110–116.
   PubMed Web of Science ®Google Scholar
• PIVNIOUK VI, MARTIN TR, LU-KUO JM et al.: SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells." Clin. Invest. (1999) 103(12):1737–1743.
   Google Scholar
• TKACZYK C, BEAVEN MA, BRACHMAN SM, METCALFE DD, GILFILLAN AM: The phospholipase C71-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase. J. Biol. Chem. (2003) 278(48):48474–48484.
   PubMed Web of Science ®Google Scholar
• SCHNEIDER H, COHEN-DAYAG A, PECHT I: Tyrosine phosphorylation of phospholipase C71 couples the Fc epsilon receptor mediated signal to mast cells secretion. hat. Immunol (1992) 4(4):447–453.
   Web of Science ®Google Scholar
• WANG D, FENG J, WEN R et al.: Phospholipase C72 is essential in the functions of B cell and several Fc receptors. Immunity (2000) 13(1):25–35.
   PubMed Web of Science ®Google Scholar
• WEN R, JOU ST, CHEN Y, HOFFMEYER A, WANG D: Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and FcyR. Immunol (2002) 169(12):6743–6752.
   Web of Science ®Google Scholar
• GARRINGTON TP, ISHIZUKA T, PAPST PJ et al: MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells. EMBO (2000) 19(20):5387–5395.
   PubMed Web of Science ®Google Scholar
• ISHIZUKA T, TERADA N, GERWINS P et al.: Mast cell tumor necrosis factor alpha production is regulated by MEK kinases. Proc. Natl. Acad. Sci.USA (1997) 94(12):6358–6363.
   PubMed Web of Science ®Google Scholar
• LORENTZ A, KLOPP I, GEBHARDT T, MANNS MP, BISCHOFF SC: Role of activator protein 1, nuclear factor-kappaB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells. J. Allergy Clin. Immunol (2003) 111(5):1062–1068.
   PubMed Web of Science ®Google Scholar
• GU H, SAITO K, KLAMAN LD et al.: Essential role for Gab2 in the allergic response. Nature (2001) 412(6843):186–190.
   PubMed Web of Science ®Google Scholar
• LEE AW, STATES DJ: Both src-dependent and -independent mechanisms mediate phosphatidylinositol 3-kinase regulation of colony-stimulating factor 1-activated mitogen-activated protein kinases in myeloid progenitors. MM. Cell Biol. (2000) 20(18):6779–6798.
   Web of Science ®Google Scholar
• OKAYAMA Y, HAGAMAN DD, METCALFE DD: A comparison of mediators released or generated by IFN-y-treated human mast cells following aggregation of FcyRI or FcERI. Immunol (2001) 166(7):4705–4712.
   Web of Science ®Google Scholar
• OKAYAMA Y, TKACZYK C, METCALFE DD, GILFILLAN AM: Comparison of FcERI- and FcyRI-mediated degranulation and TNF-alpha synthesis in human mast cells: selective utilization of phosphatidylinositol-3-kinase for Fc gamma RI-induced degranulation. Eur. Immunol (2003) 33(5):1450–1459.
   PubMed Web of Science ®Google Scholar
• •This report shows that signalling in human mast cells activated through the FcERI and FeyRI are generally similar.
   Google Scholar
• KIMURA T, ZHANG J, SAGAWA K et al.:Syk-independent tyrosine phosphorylation and association of the protein tyrosine phosphatases SHP-1 and SHP-2 with the high affinity IgE receptor. J. Immunol (1997) 159(9):4426–4434.
   PubMed Web of Science ®Google Scholar
• KIMURA T, SAKAMOTO H, APPELLA E, SIRAGANIAN RP: The negative signaling molecule 5H2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high affinity IgE receptor. J. Biol. Chem. (1997) 272(21):13991–13996.
   PubMed Web of Science ®Google Scholar
• HIRAOKA S, FURUMOTO Y, KOSEKI H et al.: Fc receptor p. subunit is required for full activation of mast cells through Fc receptor engagement. Int. Immunol (1999) 11(2):199–207.
   Google Scholar
• DOMBROWICZ D, LIN S, FLAMAND V et al: Allergy-associated FcRI3 is a molecular amplifier of IgE- and IgG-mediated in vivo responses. Immunity (1998) 8(4):517–529.
   PubMed Web of Science ®Google Scholar
• TAKATA M, HOMMA Y, KUROSAKI T: Requirement of phospholipase C72 activation in surface immunoglobulin M-induced B cell apoptosis. J. Exp. Med. (1995) 182(4):907–914.
   PubMed Web of Science ®Google Scholar
• FU C, TURCK CW, KUROSAKI T, CHAN AC: BLNK: a central linker protein in B cell activation. Immunity (1998) 9(1):93–103.
   PubMed Web of Science ®Google Scholar
• ISHIAI M, KUROSAKI M, PAPPU R et al.: BLNK required for coupling Syk to PLC72 and Racl-JNK in B cells. Immunity (1999) 10(1):117–125.
   PubMed Web of Science ®Google Scholar
• CORNALL RJ, CHENG AM, PAWSON T, GOODNOW CC: Role of Syk in B-cell development and antigen-receptor signaling. Proc. Natl. Acad. Sci. USA (2000) 97(4):1713–1718.
   PubMed Web of Science ®Google Scholar
• •This report demonstrates the role of Syk in BCR signalling in vivo.
   Google Scholar
• CHENG AM, ROWLEY B, PAO W et al: Syk tyrosine kinase required for mouse viability and B-cell development. Nature (1995) 378(6554):303–306.
   PubMed Web of Science ®Google Scholar
• ••In addition to [66], this seminal paperdescribes the haemorrhagic phenotype and B-cell developmental defect in Syk-deficient mice.
   Google Scholar
• TURNER M, MEE PJ, COSTELLO PS et al.: Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature (1995) 378(6554):298–302.
   PubMed Web of Science ®Google Scholar
• ••This is one of two pivotal papers thatdescribes the haemorrhagic phenotype and B-cell developmental defect in Syk-deficient mice.
   Google Scholar
• CLARK EA, SHATTIL SJ, GINSBERG MH, BOLEN J, BRUGGE JS: Regulation of the protein tyrosine kinase pp72syk by platelet agonists and the integrin allb133. J. Biol. Chem. (1994) 269(46):28859–28864.
   PubMed Web of Science ®Google Scholar
• TOHYAMA Y, TOHYAMA K, TSUBOKAWA M et al.: Outside-In signaling of soluble and solid-phase fibrinogen through integrin allb33 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK. Blood (1998) 92(4):1277–1286.
   PubMed Web of Science ®Google Scholar
• WOODSIDE DG, OBERGFELL A, LENG L et al.: Activation of Syk protein tyrosine kinase through interaction with integrin beta cytoplasmic domains. Can: Biol. (2001) 11(22):1799–1804.
   Google Scholar
• WOODSIDE DG, OBERGFELL A, TALAPATRA A et al.: The N-terminal 5H2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains. Biol. Chem. (2002) 277(42):39401–39408.
   Web of Science ®Google Scholar
• •This paper shows the direct interaction between Syk SH2 domains and the cytoplasmic region of P-integrins.
   Google Scholar
• SUEN PW, ILIC D, CAVEGGION E et al.: Impaired integrin-mediated signal transduction, altered cytoskeletal structure and reduced motility in Hck/Fgr deficient macrophages. Cell Sci. (1999) 112(Pt 22):4067–4078.
   PubMed Web of Science ®Google Scholar
• OBERGFELL A, ETO K, MOCSAI A et al.: Coordinate interactions of Csk, Src, and Syk kinases with ralphalllb[beta]3 initiate integrin signaling to the cytoskeleton. Cell Biol. (2002) 157(2):265–275.
   PubMed Web of Science ®Google Scholar
• ••This article shows that platelet spreadingon fibrinogen requires the sequential activation of Src and Syk. This paper also shows that Syk-/- platelets spread fully on fibrinogen when stimulated with a combination of protease-activated receptor-4 receptor-activating peptide, ADP, and epinephrine.
   Google Scholar
• MOCSAI A, LIGETI E, LOWELL CA, BERTON G: Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck. j kifnunol. (1999) 162(2):1120–1126.
   Google Scholar
• LOWELL CA, FUMAGALLI L, BERTON G: Deficiency of Src family kinases p59/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions. Cell Biol. (1996) 133(4):895–910.
   PubMed Web of Science ®Google Scholar
• PEREIRA S, ZHOU M, MOCSAI A, LOWELL C: Resting murine neutrophils express functional alpha 4 integrins that signal through Src family kinases. Immunol (2001) 166(6):4115–4123.
   Web of Science ®Google Scholar
• GAO J, ZOLLER KE, GINSBERG MH, BRUGGE JS, SHATTIL SJ: Regulation of the pp72syk protein tyrosine kinase by platelet integrin allb133. EMBO J. (1997) 16(21):6414–6425.
   PubMed Web of Science ®Google Scholar
• POOLE A, GIBBINS JM, TURNER M et al.: The Fc receptor 7-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J. (1997) 16(9):2333–2341.
   PubMed Web of Science ®Google Scholar
• •This article describes the mechanism by which collagen signals to platelets via FcRy and Syk.
   Google Scholar
• LAW DA, NANNIZZI-ALAIMO L, MINISTRI K et al: Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling in platelets. Blood (1999) 93(8):2645–2652.
   PubMed Web of Science ®Google Scholar
• ••This paper suggests that Syk is notinvolved in fibrinogen-mediated platelet adhesion and only partially involved in inside-out signalling stimulated by ADP. In addition [68] this article demonstrates that mice with Syk-deficient platelets have normal bleeding times.
   Google Scholar
• MOCSAI A, ZHANG H, JAKUS Z et al.: G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells. Blood (2003) 101(10):4155–4163.
   PubMed Web of Science ®Google Scholar
• ••This paper elegantly shows that Syk onlyplays a limited role in GPCR signalling in mast cells and neutrophils.
   Google Scholar
• BINGHAM CO, 3RD, AUSTEN KF: Mast-cell responses in the development of asthma. J. Allergy Gin. Immunol (2000) 105(2 Pt 2):S527–534.
   Google Scholar
• GURISH ME AUSTEN KF: The diverse roles of mast cells. J. Exp. Med. (2001) 194(1):F1–F5.
   PubMed Web of Science ®Google Scholar
• ZHANG J, BERENSTEIN EH, EVANS RL, SIRAGANIAN RP: Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells. J. Exp. Med. (1996) 184(1):71–79.
   PubMed Web of Science ®Google Scholar
• KEPLEY CL, YOUSSEF L, ANDREWS RP, WILSON BS, OLIVER JM: Multiple defects in Fc E RI signaling in Syk-deficient nonreleaser basophils and IL-3-induced recovery of Syk expression and secretion. j kifnunol. (2000) 165(10):5913–5920.
   Google Scholar
• KEPLEY CL, YOUSSEF L, ANDREWS RP, WILSON BS, OLIVER JM: Syk deficiency in nonreleaser basophils. J. Allergy Clin. Immunol (1999) 104(2 Pt 1):279–284.
   Google Scholar
• SYLVESTRE DL, RAVETCH JV: A dominant role for mast cell Fc receptors in the Arthus reaction. Immunity (1996) 5(4):387–390.
   PubMed Web of Science ®Google Scholar
• ZHANG Y, RAMOS BE JAKSCHIK BA: Augmentation of reverse arthus reaction by mast cells in mice. J. Clin. Invest. (1991) 88(3):841–846.
   PubMed Web of Science ®Google Scholar
• RAMOS BE ZHANG Y, ANGKACHATCHAI V, JAKSCHIK BA: Mast cell mediators regulate vascular permeability changes in Arthus reaction. Pharmacol Exp. The]: (1992) 262(2):559–565.
   PubMed Web of Science ®Google Scholar
• RAMOS BE ZHANG Y, JAKSCHIK BA: Mast cells contribute to fibrin deposition in reverse passive Arthus reaction in mouse skin. Eur. Immunol (1992) 22(9):2381–2385.
   PubMed Web of Science ®Google Scholar
• TETLOW LC, WOOLLEY DE: Distribution, activation and tryptase/ chymase phenotype of mast cells in the rheumatoid lesion. Ann. Rheum. Dis. (1995) 54(7):549–555.
   PubMed Web of Science ®Google Scholar
• TETLOW LC, WOOLLEY DE: Mast cells,cytokines, and metalloproteinases at the rheumatoid lesion: dual immunolocalisation studies. Ann. Rheum. Dis. (1995) 54(11):896–903.
   Google Scholar
• WOOLLEY DE, TETLOW LC: Mast cell activation and its relation to proinflammatory cytokine production in the rheumatoid lesion. Arthritis Res (2000) 2(1):65–74.
   PubMedGoogle Scholar
• LEE DM, FRIEND DS, GURISH MF et al.: Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science (2002) 297(5587):1689–1692.
   PubMed Web of Science ®Google Scholar
• ••This article reports definitive datademonstrating that mast cells are required for autoantibody-mediated arthritis in a murine model.
   Google Scholar
• SECOR VH, SECOR WE, GUTEKUNST CA, BROWN MA: Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J. Exp. Med. (2000) 191(5):813–822.
   PubMed Web of Science ®Google Scholar
• •This paper strongly suggests that mast cells are involved in the progression and severity of EAE.
   Google Scholar
• BARNES PJ: Cytokine-directed therapies for the treatment of chronic airway diseases. Cytokine Growth Factor Rev (2003) 14(6):511–522.
   PubMed Web of Science ®Google Scholar
• LACH-TRIFILIEFF E, MENEAR K, SCHWEIGHOFFER E, TYBULEWICZ VL, WALKER C: Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to FcyR activation. Blood (2000) 96(7):2506–2510.
   PubMed Web of Science ®Google Scholar
• •One of the first papers to assess eosinophil functions in the absence of Syk.
   Google Scholar
• QUAYLE JA, WATSON F, BUCKNALL RC, EDWARDS SW: Expression of Fc-yRIII in neutrophils in rheumatoid arthritis. Biochem. Soc. Trans. (1996) 24(3):4895.
   Google Scholar
• EDWARDS SW,WATSONF, GASMI L, MOULDING DA, QUAYLE JA: Activation of human neutrophils by soluble immune complexes: role of FcyRII and FcyRIIIb in stimulation of the respiratory burst and elevation of intracellular Ca2±. Ann. NY Acad. Sci. (1997) 832:341–357.
   PubMed Web of Science ®Google Scholar
• ABRAHAMS VM, CAMBRIDGE G, LYDYARD PM, EDWARDS JC: Induction of tumor necrosis factor alpha production by adhered human monocytes: a key role for Fcy receptor Type Ma in rheumatoid arthritis. Arthritic Rheum. (2000) 43(3):608–616.
   PubMed Web of Science ®Google Scholar
• WATSON F, GASMI L, EDWARDS SW: Stimulation of intracellular Ca2+ levels in human neutrophils by soluble immune complexes. Functional activation of FcyRIIIb during priming. I Biol. Chem. (1997) 272(29):17944–17951.
   Google Scholar
• NOSEWORTHYJH, LUCCHINETTI C, RODRIGUEZ M, WEINSHENKER BG: Multiple sclerosis. N Engl. J. Med. (2000) 343(13):938–952.
   PubMed Web of Science ®Google Scholar
• •Excellent review of the pathogenesis of MS.
   Google Scholar
• KIEFER F, BRUMELL J, AL-ALAWI N et al.: The Syk protein tyrosine kinase is essential for Fcy receptor signaling in macrophages and neutrophils. MM. Cell. Biol. (1998) 18(7):4209–4220.
   Web of Science ®Google Scholar
• •In this article, Syk-deficient macrophages and neutrophils are shown to be defective in FcyR signalling, but normal in their response to complement, LPS and IFN-y.
   Google Scholar
• MOCSAI A, ZHOU M, MENG F, TYBULEWICZ VL, LOWELL CA: Syk is required for integrin signaling in neutrophils. Immunity (2002) 16(0547–558.
   PubMed Web of Science ®Google Scholar
• •This paper reports that integrin-mediated oxidative burst in Sykl- neutrophils is defective, but not integrin-dependent haptotaxis.
   Google Scholar
• CROWLEY MT, COSTELLO PS, FITZER-ATTAS CJ et al.: A critical role for Syk in signal transduction and phagocytosis mediated by Fcy receptors on macrophages. J. Exp. Med. (1997) 186(41027–1039.
   Google Scholar
• •Syk is not required for bacterial phagocytosis or LPS signalling in macrophages despite a defect in FcyR signalling.
   Google Scholar
• BANCHEREAU J, STEINMAN RM: Dendritic cells and the control of immunity. Nature (1998) 392(6673):245–252.
   PubMed Web of Science ®Google Scholar
• REGNAULT A, LANKAR D, LACABANNE V et al: Fcy receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J. Exp. Med. (1999) 189(2):371–380.
   PubMed Web of Science ®Google Scholar
• SEDLIK C, ORBACH D, VERON Petal.: A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation. j bronunol. (2003) 170(2):846–852.
   Google Scholar
• •Evidence for the importance of Syk in &TR-mediated DC maturation and antigen presentation in response to ICs.
   Google Scholar
• DE VITA S, ZAJA F, SACCO S et al.: Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells. Arthritis Rheum. (2002) 46(8):2029–2033.
   PubMed Web of Science ®Google Scholar
• SILVERMAN GJ, WEISMAN S: Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy. Arthritis Rheum. (2003) 48(6):1484–1492.
   PubMed Web of Science ®Google Scholar
• PROTHEROE A, EDWARDS JC, SIMMONS A, MACLENNAN K, SELBY P: Remission of inflammatory arthropathy in association with anti-CD20 therapy for non-Hodgkin's lymphoma. Rheurnatology (Oxford) (1999) 38(11):1150–1152.
   PubMed Web of Science ®Google Scholar
• TEDDER TF, ENGEL P: CD20: a regulator of cell-cycle progression of B lymphocytes. Bronunol. Today (1994) 15(9):450–454.
   PubMedGoogle Scholar
• CAMBRIDGE G, LEANDRO MJ, EDWARDS JC et al: Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritic Rheum. (2003) 48(8):2146–2154.
   PubMed Web of Science ®Google Scholar
• EDWARDS JC, LEANDRO MJ, CAMBRIDGE G: B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune disorders. Biochem. Soc. Trans. (2002) 30(4):824–828.
   PubMedGoogle Scholar
• JIANG K, ZHONG B, GILVARY DL et al.: Syk regulation of phosphoinositide 3-kinase-dependent NK cell function. Immunol (2002) 168(7):3155–3164.
   Web of Science ®Google Scholar
• LANIER LL, CORLISS BC, WU J, LEONG C, PHILLIPS JH: Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature (1998) 391(6668):703–707.
   PubMed Web of Science ®Google Scholar
• ZOMPI S, HAMERMAN JA, OGASAWARA K et al.: NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat. Immun.ol (2003) 4(6):565–572.
   PubMed Web of Science ®Google Scholar
• •See [103].
   Google Scholar
• COLUCCI F, SCHWEIGHOFFER E, TOMASELLO E et al.: Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases. Nat. Immunol (2002) 3(3):288–294.
   PubMed Web of Science ®Google Scholar
• •These papers discuss that NK-mediated tumour cytotoxicity is not dependent on Syk.
   Google Scholar
• LANIER LL: Natural killer cell receptor signaling. Can: Opin. Immunol. (2003) 15(3):308–314.
   PubMed Web of Science ®Google Scholar
• BAUER M, MASCHBERGER P, QUEK L et al.: Genetic and pharmacological analyses of involvement of Src-family, Syk and Btk tyrosine kinases in platelet shape change. Src-kinases mediate integrin aIIb 33 inside-out signalling during shape change. Thromb. Haemost. (2001) 85(2):331–340.
   Google Scholar
• ICHINOHE T, TAKAYAMA H, EZUMI Y et al.: Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI. J. Biol. Chem. (1997) 272(1):63–68.
   PubMed Web of Science ®Google Scholar
• ICHINOHE T, TAKAYAMA H, EZUMI Y et al.: Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI. ./. Biol. Chem. (1995) 270(47):28029–28036.
   PubMed Web of Science ®Google Scholar
• YANAGI S, INATOME R, DING Jet al.: Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice. Blood (2001) 98(9):2869–2871.
   Google Scholar
• RAFII S, SKOBE M: Splitting vessels: keeping lymph apart from blood. Nat. Med. (2003) 9(2):166–168.
   PubMed Web of Science ®Google Scholar
• •An excellent short review of the role of Syk in vascular and lymphatic vessel development.
   Google Scholar
• MOROI M, JUNG SM, OKUMA M, SHINMYOZU K: A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. Clin. Invest. (1989) 84(5):1440–1445.
   Google Scholar
• INATOME R, YANAGI S, TAKANO T, YAMAMURA H: A critical role for Syk in endothelial cell proliferation and migration. Biochem. Biophys. Res. Commun. (2001) 286(1):195–199.
   PubMed Web of Science ®Google Scholar
• JAIN RK, PADERA TP: Development. Lymphatics make the break. Science (2003) 299(5604):209–210.
   Google Scholar
• •An excellent short review of the role of Syk in vascular and lymphatic vessel development.
   Google Scholar
• COLUCCI F, TURNER M, SCHWEIGHOFFER E et al.: Redundant role of the Syk protein tyrosine kinase in mouse NK cell differentiation.' Immunol. (1999) 163(4):1769–1774.
   Web of Science ®Google Scholar
• CHAMBERS TI: Multinucleate giant cells. Pathol. (1978) 126(3):125–148.
   Web of Science ®Google Scholar
• WONG BR, JOSIEN R, LEE SY et al.: TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. Exp. Med. (1997) 186(12):2075–2080.
   PubMed Web of Science ®Google Scholar
• ANDERSON DM, MARASKOVSKY E, BILLINGSLEY WL et al.: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature (1997) 390(6656):175–179.
   PubMed Web of Science ®Google Scholar
• YASUDA H, SHIMA N, NAKAGAWA N et al.: Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Nati Acad. Sci. USA (1998) 95(7):3597–3602.
   PubMed Web of Science ®Google Scholar
• LACEY DL, TIMMS E, TAN HL et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell (1998) 93(2):165–176.
   PubMed Web of Science ®Google Scholar
• CHAMBERS TJ: Regulation of the differentiation and function of osteoclasts. Pathol. (2000) 192(1):4–13.
   Web of Science ®Google Scholar
• BOYLE WJ, SIMONET WS, LACEY DL: Osteoclast differentiation and activation. Nature (2003) 423(6937):337–342.
   PubMed Web of Science ®Google Scholar
• KOGA T, INUI M, INOUE K et al.: Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature (2004) 428(6984):758–763.
   PubMed Web of Science ®Google Scholar
• •Describes the importance of the ITAIVI-bearing receptors DAP12 and FcRy in osteodast differentiation.
   Google Scholar
• MOCSAI A, HUMPHREY MB, VAN ZIFFLE JA et al.: The immunomodulatory adapter proteins DAP12 and Fc receptor 7-chain (FcRy) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc. Natl. Acad. Sci. USA (2004) 101(16):6158–6163.
   Google Scholar
• ••Key paper demonstrating the role of Syk in osteoclastogenesis.
   Google Scholar
• KAIFU T, NAKAHARA J, INUI M et al.: Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. Clin. Invest. (2003) 111(3):323–332.
   Google Scholar
• FACCIO R, ZOU W, COLAIANNI G, TEITELBAUM SL, ROSS FP: High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype.Biochem. (2003) 90(5):871–883.
   Web of Science ®Google Scholar
• GOLD MR: To make antibodies or not: signaling by the B-cell antigen receptor. Trends Pharmacol. Sci. (2002) 23(7):316–324.
   PubMed Web of Science ®Google Scholar
• POGUE SL, KUROSAKI T, BOLEN J, HERBST R: B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase. Immunol. (2000) 165(3):1300–1306.
   Web of Science ®Google Scholar
• KALESNIKOFF J, HUBER M, LAM V et al.: Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity (2001) 14(6):801–811.
   PubMed Web of Science ®Google Scholar
• KITAURA J, SONG J, TSAI M et al: Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI. Proc. Nati Acad. Sci USA (2003) 100(22):12911–12916.
   PubMed Web of Science ®Google Scholar
• GOLD MR, SCHEID MP, SANTOS L et al.: The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. I Immunol. (1999) 163(4):1894–1905.
   PubMed Web of Science ®Google Scholar
• KITAURA J, ASAI K, MAEDA-YAMAMOTO M et al.: Akt-dependent cytokine production in mast cells. Exp. Med. (2000) 192(5):729–740.
   PubMed Web of Science ®Google Scholar
• LUO J, MANNING BD, CANTLEY LC: Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell (2003) 4(4):257–262.
   PubMed Web of Science ®Google Scholar
• LAWLOR MA, ALESSI DR: PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? Cell Sci. (2001) 114(Pt 16):2903–2910.
   Google Scholar
• KUNO Y, ABE A, EMI N et al.: Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12) (q22;p12). Blood (2001) 97(4):1050–1055.
   PubMed Web of Science ®Google Scholar
• KANIE T, ABE A, MATSUDA T et al.: TEL-Syk fusion constitutively activates P13-K/Akt, MAPK and JAK2-independent STAT5 signal pathways. Leukemia (2004) 18(3):548–555.
   PubMed Web of Science ®Google Scholar
• LAGUNOFF M, LUKAC DM, GANEM D: Immunoreceptor tyrosine-based activation motif-dependent signaling by Kaposi's sarcoma-associated herpesvirus K1 protein: effects on lytic viral replication. Virol. (2001) 75(13):5891–5898.
   Web of Science ®Google Scholar
• TOMLINSON CC, DAMANIA B: The K1 protein of Kaposi's sarcoma-associated herpesvirus activates the Akt signaling pathway. Vim] (2004) 78(4):1918–1927.
   Google Scholar
• LEE H, VEAZEY R, WILLIAMS K et al.: Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus. Nat Med (1998) 4(4):435–440.
   PubMed Web of Science ®Google Scholar
• MERCHANT M, CALDWELL RG, LONGNECKER R: The LMP2A ITAM is essential for providing B cells with development and survival signals M viva Virol (2000) 74(19):9115–9124.
   Google Scholar
• CALDWELL RG, WILSON JB, ANDERSON SJ, LONGNECKER R: Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Iminunig, (1998) 9(3):405–411.
   PubMed Web of Science ®Google Scholar
• PORTIS T, COOPER L, DENNIS P, LONGNECKER R: The LMP2A signalosome-a therapeutic target for Epstein-Barr virus latency and associated disease. Front. BioscL (2002) 7:d414–d426.
   PubMed Web of Science ®Google Scholar
• COOPER L, LONGNECKER R: Inhibition of host kinase activity altered by the LMP2A signalosome-a therapeutic target for Epstein-Barr virus latency and associated disease. Antiviral Res. (2002) 56(3):219–231.
   PubMed Web of Science ®Google Scholar
• COOPMAN PJ, DO MT, BARTH M et al.: The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature (2000) 406(6797):742–747.
   PubMed Web of Science ®Google Scholar
• •The first paper to suggest that Syk may play a role in suppressing breast cancer growth.
   Google Scholar
• FLUCK M, ZURCHER G, ANDRES AC, ZIEMIECKI A: Molecular characterization of the murine syk protein tyrosine kinase cDNA, transcripts and protein. Biochein. Biophys. Res. Commun. (1995) 213(1):273–281.
   PubMed Web of Science ®Google Scholar
• •This report demonstrated that the Syk expression seen in breast tissue is mainly restricted to local lymphoid tissue and not in the breastper se. In addition, this article reports that Syk is overexpressed in aggressive tumours and poorly expressed in less malignant tumours.
   Google Scholar
• ROSS DT, SCHERF U, EISEN MB et al.: Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. (2000) 24(3):227–235.
   PubMed Web of Science ®Google Scholar
• ••Performed a genome wide expressionanalysis to show heterogeneity in breast cancer cell lines.
   Google Scholar
• THOMPSON EW, PAIK S, BRUNNER Net al.: Association of increased basementmembrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J. Cell. Physiol (1992) 150(3):534–544.
   Google Scholar
• SOMMERS CL, BYERS SW, THOMPSON EW, TORRI JA, GELMANN EP: Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res. Treat. (1994) 31(2-3):325–335.
   PubMed Web of Science ®Google Scholar
• PEROU CM, SORLIE T, EISEN MB et al: Molecular portraits of human breast tumours. Nature (2000) 406(6797):747–752.
   PubMed Web of Science ®Google Scholar
• VAN DE VIJVER MJ, HE YD, VAN'T VEER LJ et al.: A gene-expression signature as a predictor of survival in breast cancer. N Engl.' Med. (2002) 347(25):1999–2009.
   Google Scholar
• VAN 'T VEER LJ, DAI H, VAN DE VIJVER MJ et al.: Gene expression profiling predicts clinical outcome of breast cancer. Nature (2002) 415(6871)530–536.
   Google Scholar
• TOYAMA T, IWASE H, YAMASHITA H et al: Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer. Cancer Lett. (2003) 189(1):97–102.
   PubMed Web of Science ®Google Scholar
• TRICARICO C, PINZANI P, BIANCHI S et al.: Quantitative real-time reverse transcription polymerase chain reaction: normalization to rRNA or single housekeeping genes is inappropriate for human tissue biopsies. Anal. Biochem. (2002) 309(2):293–300.
   PubMed Web of Science ®Google Scholar
• WILLIAMS CM, GALLI SJ: Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. I Exp. Med. (2000) 192(3):455–462.
   PubMed Web of Science ®Google Scholar
• ••This provides an excellent overview of therole of the mast cell in murine asthma models.
   Google Scholar
• KOBAYASHI T, MIURA T, HABA T et al.: An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model.,/ Immunol (2000) 164(7):3855–3861.
   PubMed Web of Science ®Google Scholar
• BRIGHTLING CE, BRADDING P, SYMON FA et al.: Mast-cell infiltration of airway smooth muscle in asthma. N Engl. Med. (2002) 346(22):1699–1705.
   PubMed Web of Science ®Google Scholar
• •An important study examining the localisation of mast cells in asthmatic patients.
   Google Scholar
• BABU KS, HOLGATE ST: The role of anti-IgE therapies in the treatment of asthma. Hosp. Med (2002) 63(8):483–486.
   PubMed Web of Science ®Google Scholar
• FREW AJ: Effects of anti-IgE in asthmatic subjects. Thorax (1998) 53\(Suppl. 2):552–557.
   Google Scholar
• MAYR SI, ZUBERI RI, ZHANG M et al.: IgE-dependent mast cell activation potentiates airway responses in murine asthma models. 1 Immunol (2002) 169(4):2061–2068.
   Google Scholar
• STENTON GR, ULANOVA M, DERY RE et al.: Inhibition of allergic inflammation in the airways using aerosolized antisense to Syk kinase. Immunol (2002) 169(2):1028–1036.
   Web of Science ®Google Scholar
• ••Direct evidence for the role of Syk in thepathogenesis of asthma.
   Google Scholar
• SEWELL WA, SCURR LL, ORPHANIDES H, KINDER S, LUDOWYKE RI: Induction of interleukin-4 and interleukin-5 expression in mast cells is inhibited by glucocorticoids. Diagn. Lab. Immunol (1998) 5(1):18–23.
   PubMedGoogle Scholar
• KYBURZ D, CORR M: The KRN mouse model of inflammatory arthritis. Springer Semin. Immunopathol (2003) 25(1):79–90.
   PubMed Web of Science ®Google Scholar
• KAGARI T, TANAKA D, DOI H, SHIM OZATO T: Essential role of Fc gamma receptors in anti-type II collagen antibody-induced arthritis. I Immunol (2003) 170(8):4318–4324.
   PubMed Web of Science ®Google Scholar
• NANDAKUMAR KS, ANDREN M, MARTINSSON P et al.: Induction of arthritis by single monoclonal IgG anti-collagen Type II antibodies and enhancement of arthritis in mice lacking inhibitory FcyRIIB. Eur.j Immunol (2003) 33(8):2269–2277.
   PubMed Web of Science ®Google Scholar
• KLEINAU S, MARTINSSON P, HEYMAN B: Induction and suppression of collagen-induced arthritis is dependent on distinct fcy receptors. Exp. Med. (2000) 191(9):1611–1616.
   PubMed Web of Science ®Google Scholar
• •Collagen-induced arthritis is dependent on
   Google Scholar
• DIAZ DE STAHL T, ANDREN M, MARTINSSON P, VERBEEK JS, KLEINAU S: Expression of FcgammaRIII is required for development of collagen-induced arthritis. Ear: I Immunol (2002) 32(102915–2922.
   Google Scholar
• KYOGOKU C, TSUCHIYA N, MATSUTA K, TOKUNAGA K: Studies on the association of Fcy receptor IIA, IIB, IIIA and IIIB polymorphisms with rheumatoid arthritis in the Japanese: evidence for a genetic interaction between HLA-DRB1 and FC7R3A. Genes Immun (2002) 3(8):488–493.
   PubMed Web of Science ®Google Scholar
• MORGAN AW, GRIFFITHS B, PONCHEL F et al: Fcy receptor Type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups. Arthritis Rheum. (2000) 43(10):2328–2334.
   PubMed Web of Science ®Google Scholar
• STEINMAN L, ZAMVIL S: Transcriptional analysis of targets in multiple sclerosis. Nat. Rev Immunol. (2003) 3(6):483–492.
   PubMed Web of Science ®Google Scholar
• •An informative review of data pointing to an allergic component to MS.
   Google Scholar
• LOCK C, HERMANS G, PEDOTTI R et al.: Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. (2002) 8(5):500–508.
   PubMed Web of Science ®Google Scholar
• •Indicates several genes upregulated in MS lesions are involved in the allergic response.
   Google Scholar
• PEDOTTI R, DEVOSS JJ, YOUSSEF S et al.: Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. Proc. Natl. Acad. Sci. USA (2003) 100(4):1867–1872.
   PubMed Web of Science ®Google Scholar
• ROBBIE-RYAN M, TANZOLA MB, SECOR VH, BROWN MA: Cutting edge: both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephalomyelitis disease severity.' Immunol. (2003) 170(4):1630–1634.
   Web of Science ®Google Scholar
• •This is a key paper demonstrating that FcyRs on mast cells are critical for the development of EAE.
   Google Scholar
• MANGER K, REPP R, SPRIEWALD BM et al.: Fcy receptor Ha polymorphism in Caucasian patients with systemic lupus erythematosus: association with clinical symptoms. Arthritis Rheum. (1998) 41(7):1181–1189.
   PubMed Web of Science ®Google Scholar
• YEE AM, NG SC, SOBEL RE, SALMON JE: FcyRIIA polymorphism as a risk factor for invasive pneumococcal infections in systemic lupus erythematosus. Arthritis Rheum. (1997) 40(6):1180–1182.
   PubMed Web of Science ®Google Scholar
• KARASSA FB, TRIKALINOS TA, IOANNIDIS JP: Role of the Fcy receptor Ik polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis Rheum. (2002) 46(6):1563–1571.
   PubMed Web of Science ®Google Scholar
• EDBERG JC, LANGEFELD CD, WU J et al.: Genetic linkage and association of FcyRIIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus. Arthritis Rheum. (2002) 46(8):2132–2140.
   PubMed Web of Science ®Google Scholar
• WU J, EDBERG JC, REDECHA PB et al.: A novel polymorphism of FcyRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. Clin. Invest. (1997) 100(5):1059–1070.
   Google Scholar
• KARASSA FB, TRIKALINOS TA, IOANNIDIS JP: The FcyRIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis. Kidney Int. (2003) 63(4):1475–1482.
   PubMed Web of Science ®Google Scholar
• KOENE HR, KLEIJER M, SWAAK AJ et al: The FcyRIIIA-158F allele is a risk factor for systemic lupus erythematosus. Arthritis Rheum. (1998) 41(10):1813–1818.
   PubMed Web of Science ®Google Scholar
• CLYNES R, DUMITRU C, RAVETCH JV: Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science (1998) 279(5353):1052–1054.
   PubMed Web of Science ®Google Scholar
• ••Seminal paper demonstrating the criticalrole of the FcR-7 chain in autoimmune nephritis.
   Google Scholar
• PARK SY, UEDA S, OHNO H et al: Resistance of Fc receptor- deficient mice to fatal glomerulonephritis. j Clin. Invest. (1998) 102(6):1229–1238.
   PubMed Web of Science ®Google Scholar
• FUJII T, HAMANO Y, UEDA S et al.: Predominant role of FcyRIII in the induction of accelerated nephrotoxic glomerulonephritis. Kidney Int. (2003) 64(4):1406–1416.
   PubMed Web of Science ®Google Scholar
• •Shows that FeyRIII is primarily responsible for IC-mediated glomerulonephritis.
   Google Scholar
• NATHAN C: Points of control in inflammation. Nature (2002) 420(6917):846–852.
   PubMed Web of Science ®Google Scholar
• FIRESTEIN GS: Evolving concepts of rheumatoid arthritis. Nature (2003) 423(6937):356–361.
   PubMed Web of Science ®Google Scholar
• BUCKBINDER L: The glucocorticoid receptor: molecular mechanisms and new therapeutic opportunities. Inflamm. Res. (2002) 51(4):167–169.
   PubMedGoogle Scholar
• NIIMI T, ORITA M, OKAZAWA-IGARASHI M et al.: Design and synthesis of non-peptidic inhibitors for the Syk C-terminal 5H2 domain based on structure-based in-silico screening. Med. Chem. (2001) 44(26):4737–4740.
   Web of Science ®Google Scholar
• MORIYA K, RIVERA J, ODOM S et a/.: ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk. Proc. Nati Acad. Sci. USA (1997) 94(23):12539–12544.
   Google Scholar
• CYVVIN CL, ZHAO BP, MCNEIL DW et al.: Discovery and SAR of novel Naphthyridines as potent inhibitors of spleen tyrosine kinase (SYK). Bioorg. Med. Chem. Lett (2003) 13(8):1415–1418. zoo. LAI JY, COX PJ, PATEL R et al.: Potent small molecule inhibitors of spleen tyrosine kinase (Syk). Bioorg. Med. Chem. Lett (2003) 13(18):3111–3114. an. YAMAMOTO N, TAKESHITA K, SHICHIJO M et al.: The orally available spleen tyrosine kinase inhibitor 2- [743,4-dimethoxypheny1)-imidazo [1,2-c]pyrimidin-5-ylaminolnicotinamide dihydrochloride (BAY 61–3606) blocks antigen-induced airway inflammation in rodents. Pharmacol. Exp. Ther. (2003) 306(3):1174–1181.
   Google Scholar
• KELLY HW: Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids. Ann. Allergy Asthma Immunol. (2003) 91(4):326–334.
   PubMed Web of Science ®Google Scholar
• MOHAMMED SP, TAYLOR CV, WEYMAN-JONES CB et al.: Duration of action of inhaled versus Intravenous beta(2)-adrenoceptor agonists in an anaesthetized guinea-pig model. Palm. Pharmacol. The]: (2000) 13(6):287–292.
   PubMed Web of Science ®Google Scholar
• GUYER B, SHIMAMOTO S, BRADHURST A et al.: The effect of a novel inihibitor of mast cell activation on mediators, symptoms and nasal patency in allergic rhinitis. I Allergy Clin. Immunol. (2004) 113(2):528–529.
   PubMedGoogle Scholar
• ••First evidence for clinical safety andefficacy of a topical Syk inhibitor.
   Google Scholar