Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 17, 2008 - Issue 5
Submit an article Journal homepage
435
Views
49
CrossRef citations to date
0
Altmetric
Reviews

Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis

Malini Bajpai Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India +91 124 2342001 10, ext: 5256; +91 124 [email protected]
, PhD,
Puneet Chopra Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India +91 124 2342001 10, ext: 5256; +91 124 [email protected]
, PhD,
Sunanda G Dastidar Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India +91 124 2342001 10, ext: 5256; +91 124 [email protected]
, PhD &
Abhijit Ray Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India +91 124 2342001 10, ext: 5256; +91 124 [email protected]
, PhD
Pages 641-659 | Published online: 30 Apr 2008

Bibliography

  • Gabriel SE, Crowson CS, Kremers HM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 2003;48(1):54-8
  • Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 2001;27(2):269-81
  • Olsen NJ, Stein CM. New Drugs for rheumatoid arthritis. N Engl J Med 2004;350:2167-79
  • Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 2006;319(3):998-1008
  • Cha HS, Boyle DL, Inoue T, et al. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther 2006;317(2):571-8
  • Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nature review. Drug Discov 2003;2:473-88
  • Schulze-Koops H, Kalden JR. The balance of Th1/Th2 cytokines in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2001;15(5):677-91
  • Park JY, Pillinger MH. Interleukin-6 in the pathogenesis of rheumatoid arthritis. Bull NYU Hosp Joint Dis 2007;65(Suppl 1):S4-10
  • Sivalingam SP, Thumboo J, Vasoo S, et al. In vivo pro- and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis. Ann Acad Med Singapore 2007;36(2):96-9
  • Petrovic-Rackov L, Pejnovic N. Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis. Clin Rheumatol 2006;25(4):448-2
  • Andreakos E, Sacre S, Foxwell BM, Feldmann M. The toll-like receptor-nuclear factor kappaB pathway in rheumatoid arthritis. Front Biosci 2005;10:2478-88
  • Weber C. Novel mechanistic concepts for the control of leukocyte transmigration: specialization of integrins, chemokines, and junctional molecules. J Mol Med 2003;81(1):4-19
  • Zvaifler NJ, Firestein GS. Pannus and pannocytes. Alternative models of joint destruction in rheumatoid arthritis. Arthritis Rheum 1994;37(6):783-9
  • Teitelbaum SL. Bone resorption by osteoclasts. Science 2000;289(5484):1504-8
  • Rannou F, François M, Corvol MT, Berenbaum F. Cartilage breakdown in rheumatoid arthritis. Joint Bone Spine 2006;73(1):29-36
  • Isomäki P, Punnonen J. Pro- and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med 1997;29(6):499-507
  • St Clair EW, Van Der Heijde DM, Smolen JS, et al. Active-controlled study of patients receiving infliximab for the treatment of rheumatoid arthritis of early onset study group. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50(11):3432-43
  • Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48(1):35-45. Erratum in: Arthritis Rheum 2003;48(3):855
  • van der Heijde D, Klareskog L, Landewé R, et al. Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2007;56(12):3928-39
  • Gómez-Reino JJ, Carmona L, Valverde VR, et al. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 2003;48(8):2122-7
  • Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum 2004;50(6):1740-51
  • Solau-Gervais E, Laxenaire N, Cortet B, et al. Lack of efficacy of a third tumour necrosis factor alpha antagonist after failure of a soluble receptor and a monoclonal antibody. Rheumatology (Oxford) 2006;45(9):1121-4
  • Thabet MM, Huizinga TW. Drug evaluation: apratastat, a novel TACE/MMP inhibitor for rheumatoid arthritis. Curr Opin Investig Drugs 2006;7(11):1014-9
  • Horai R, Saijo S, Tanioka H, et al. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med 2000;191(2):313-20
  • Joosten LA, Helsen MM, Saxne T, et al. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol 1999;163(9):5049-55
  • Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002;46(3):614-24
  • Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65(8):1006-12
  • Siegmund B, Zeitz M. Pralnacasan (vertex pharmaceuticals). IDrugs 2003;6(2):154-8
  • Hata H, Sakaguchi N, Yoshitomi H, et al. Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 2004;114(4):582-8
  • Woo P, Wilkinson N, Prieur AM, et al. Open label Phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 2005;7(6):1281-8
  • Baslund B, Tvede N, Danneskiold-Samsoe B, et al. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum 2005;52(9):2686-92
  • Plater-Zyberk C, Joosten LA, Helsen MM, et al. Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis. J Clin Invest 2001;108(12):1825-32
  • Olsen NJ, Brooks RH, Cush JJ, et al. A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. Arthritis Rheum 1996;39(7):1102-8. Erratum in: Arthritis Rheum 1996;39(9):1575
  • Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350(25):2572-81
  • Higashida J, Wun T, Schmidt S, et al. Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol 2005;32(11):2109-15
  • Listing J, Strangfeld A, Kary S, et al. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 2005;52(11):3403-12
  • Feng Y, Schreiner GF, Chakravarty S, et al. Inhibition of the mitogen activated protein kinase, p38 alpha, prevents proinflammatory cytokine induction by human adherent mononuclear leukocytes in response to lipid loading. Atherosclerosis 2001;158(2):331-8
  • Dominguez C, Powers DA, Tamayo N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Dev 2005;8(4):421-30
  • Walker JG, Ahern MJ, Coleman M, et al. Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis. Ann Rheum Dis 2007;66(8):992-9
  • Kyburz D, Corr M. The KRN mouse model of inflammatory arthritis. Springer Semin Immunopathol 2003;25(1):79-90
  • Kleinau S, Martinsson P, Heyman B. Induction and suppression of collagen-induced arthritis is dependent on distinct fcgamma receptors. J Exp Med 2000;191(9):1611-6
  • Andrén M, Xiang Z, Nilsson G, Kleinau S. FcgammaRIII-expressing macrophages are essential for development of collagen-induced arthritis. Scand J Immunol 2006;63(4):282-9
  • P Mark Hogarth. Fc receptors are major mediators of antibody based inflammation in autoimmunity. Curr Opin Immunol 2002;14:798-802
  • Van Lent PL, Grevers L, Lubberts E, et al. Fcgamma receptors directly mediate cartilage, but not bone, destruction in murine antigen-induced arthritis: uncoupling of cartilage damage from bone erosion and joint inflammation. Arthritis Rheum 2006;54(12):3868-77
  • Nandakumar KS, Andrén 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 FcgammaRIIB. Eur J Immunol 2003;33(8):2269-77
  • Monach P, Hattori K, Huang H, et al. The K/BxN mouse model of inflammatory arthritis: theory and practice. Methods Mol Med 2007;136:269-82
  • Wong BR, Grossbard EB, Payan DG, Masuda ES. Targeting Syk as a treatment for allergic and autoimmune disorders. Exper Opin Investig Drugs 2004;13(7):743-62
  • Ulanova M, Duta F, Puttagunta L, et al. Spleen tyrosine kinase (Syk) as a novel target for allergic asthma and rhinitis. Expert Opin Ther Targets 2005;9(5):901-21
  • Sada K, Takano T, Yanagi S, Yamamura H. Structure and function of Syk protein-tyrosine kinase. J Biochem 2001;130(2):177-86
  • 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. J Immunol 1998;161(10):5276-83
  • 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. J Biol Chem 2000;275(45):35442-7
  • Humphrey MB, Lanier LL, Nakamura MC. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev 2005;208:50-65
  • Lin S, Cicala C, Scharenberg AM, Kinet JP. The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals. Cell 1996;85(7):985-95
  • 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. J Biol Chem 1996;271(44):27962-8
  • Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 2008;8(1):34-47
  • 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):2595-605
  • Teramoto H, Salem P, Robbins KC, et al. Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway. J Biol Chem 1997;272(16):10751-5
  • 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
  • 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):669-82
  • Pasquet JM, Gross B, Quek L, et al. LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Mol Cell Biol 1999;19(12):8326-34
  • Pivniouk VI, Martin TR, Lu-Kuo JM, et al. SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. J Clin Invest 1999;103(12):1737-43
  • Wen R, Jou ST, Chen Y, et al. Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R. J Immunol 2002;169(12):6743-52
  • Lorentz A, Klopp I, Gebhardt T, et al. 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):1062-8
  • Okayama Y, Hagaman DD, Metcalfe DD. A comparison of mediators released or generated by IFN-gamma-treated human mast cells following aggregation of Fc gamma RI or Fc epsilon RI. J Immunol 2001;166(7):4705-12
  • Mócsai A, Abram CL, Jakus Z, et al. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol 2006;7:1326-33
  • Woodside DG, Obergfell A, Talapatra A, et al. The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains. J Biol Chem 2002;277(42):39401-8
  • Obergfell A, Eto K, Mocsai A, et al. Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. J Cell Biol 2002;157(2):265-75
  • Gao J, Zoller KE, Ginsberg MH, et al. Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3. EMBO J 1997;16(21):6414-25
  • Poole A, Gibbins JM, Turner M, et al. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 1997;16(9):2333-41
  • Mócsai A, Zhang H, Jakus Z, et al. G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells. Blood 2003;101(10):4155-63
  • Lanier LL, Corliss BC, Wu J, et al. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 1998;391(6668):703-7
  • Mócsai A, Humphrey MB, Van Ziffle JA, et al. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci 2004;101(16):6158-63
  • Cornall RJ, Cheng AM, Pawson T, Goodnow CC. Role of Syk in B-cell development and antigen-receptor signaling. Proc Natl Acad Sci 2000;97(4):1713-8
  • Takada Y, Aggarwal BB. TNF activates Syk protein tyrosine kinase leading to TNF-induced MAPK activation, NF-kappaB activation, and apoptosis. J Immunol 2004;173(2):1066-77
  • Arndt PG, Suzuki N, Avdi NJ, et al. Lipopolysaccharide-induced c-Jun NH2-terminal kinase activation in human neutrophils: role of phosphatidylinositol 3-Kinase and Syk-mediated pathways. J Biol Chem 2004;279(12):10883-91
  • Avdi NJ, Nick JA, Whitlock BB, et al. Tumor necrosis factor-alpha activation of the c-Jun N-terminal kinase pathway in human neutrophils. Integrin involvement in a pathway leading from cytoplasmic tyrosine kinases apoptosis. J Biol Chem 2001;276(3):2189-99
  • Gurish MF, Austen KF. The diverse roles of mast cells. J Exp Med 2001;194(1):1-5
  • Sylvestre DL, Ravetch JV. A dominant role for mast cell Fc receptors in the Arthus reaction. Immunity 1996;5(4):387-90
  • Ramos BF, Zhang Y, Angkachatchai V, Jakschik BA. Mast cell mediators regulate vascular permeability changes in Arthus reaction. J Pharmacol Exp Ther 1992;262(2):559-65
  • 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
  • Lee DM, Friend DS, Gurish MF, et al. Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 2002;297(5587):1689-92
  • Quayle JA, Watson F, Bucknall RC, Edwards SW. Expression of Fc gamma RIII in neutrophils in rheumatoid arthritis. Biochem Soc Trans 1996;24(3):489S
  • Watson F, Gasmi L, Edwards SW. Stimulation of intracellular Ca2+ levels in human neutrophils by soluble immune complexes. Functional activation of FcgammaRIIIb during priming. J Biol Chem 1997;272(29):17944-51
  • Mócsai A, Zhou M, Meng F, et al. Syk is required for integrin signaling in neutrophils. Immunity 2002;16(4):547-58
  • Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392(6673):245-52
  • Sedlik C, Orbach D, Veron P, et al. A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation. J Immunol 2003;170(2):846-52
  • Cheng AM, Rowley B, Pao W, et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 1995;378(6554):303-6
  • Fu C, Turck CW, Kurosaki T, Chan AC. BLNK: a central linker protein in B cell activation. Immunity 1998;9(1):93-103
  • Ishiai M, Kurosaki M, Pappu R, et al. BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. Immunity 1999;10(1):117-25
  • Ishiai M, Sugawara H, Kurosaki M, Kurosaki T. Cutting edge: association of phospholipase C-gamma 2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signaling. J Immunol 1999;163(4):1746-9
  • Cambridge G, Leandro MJ, Edwards JC, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 2003;48(8):2146-54
  • Krishnan S, Farber DL, Tsokos GC. T cell rewiring in differentiation and disease. J Immunol 2003;171(7):3325-31
  • 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):175-9
  • Nakagawa N, Kinosaki M, Yamaguchi K, et al. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun 1998;253(2):395-400
  • Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423(6937):337-42
  • 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):758-63
  • Faccio R, Zou W, Colaianni G, et al. High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. J Cell Biochem 2003;90(5):871-83
  • Colucci F, Schweighoffer E, Tomasello E, et al. Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases. Nat Immunol 2002;3(3):288-94
  • Yamamoto N, Takeshita K, Shichijo M, et al. The orally available spleen tyrosine kinase inhibitor 2-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]nicotinamide dihydrochloride (BAY 61-3606) blocks antigen-induced airway inflammation in rodents. J Pharmacol Exp Ther 2003;306(3):1174-81
  • Masuda ES, Schmitz J. Syk inhibitors as treatment for allergic rhinitis Pulm Pharmacol Ther 2007 [Epub ahead of print]
  • Pine PR, Chang B, Schoettler N, et al. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol 2007;124(3):244-57
  • Zhu Y, Herlaar E, Masuda ES, et al. Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406. Toxicol Appl Pharmacol 2007;221(3):268-77
  • Crnkic M, Månsson B, Larsson L, et al. Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoid arthritis patients treated with infliximab or etanercept. Arthritis Res Ther 2003;5(4):181-5
  • Joosten LA, Smeets RL, Koenders MI, et al. Interleukin-18 promotes joint inflammation and induces interleukin-1-driven cartilage destruction. Am J Pathol 2004;165(3):959-67
  • Palmqvist P, Persson E, Conaway HH, Lerner UH. IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J Immunol 2002;169(6):3353-62
  • Strand V, Kavanaugh AF. The role of interleukin-1 in bone resorption in rheumatoid arthritis. Rheumatology 2004;43(Suppl 3):iii10-6
  • Rigel Website-Home page. Available from: www.rigel.com
  • 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):195-9
  • Jain RK, Padera TP. Development. Lymphatics make the break. Science 2003;299(5604):209-10
  • Yanagi S, Inatome R, Ding J, et al. Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice. Blood 2001;98(9):2869-71
  • Rafii S, Skobe M. Splitting vessels: keeping lymph apart from blood. Nat Med 2003;9(2):166-8
  • 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):247-51
  • Yanagi S, Inatome R, Takano T, Yamamura H. Syk expression and novel function in a wide variety of tissues. Biochem Biophys Res Commun 2001;288(3):495-8
  • Hamerman JA, Tchao NK, Lowell CA, Lanier LL. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat Immunol 2005;6(6):579-86
  • Coopman PJ, Mueller SC. The Syk tyrosine kinase: a new negative regulator in tumor growth and progression. Cancer Lett 2006;241(2):159-73
  • Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 2000;24(3):227-35

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.