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Cytokine Receptors and Signaling

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Immunopharmacology

Abstract

Cytokines exert their effects after binding to specific cell surface receptors, which are composed of polypeptide chains. After the binding of the ligand to its receptor, there is an initiation of the signal transduction pathways culminating in the synthesis of new mRNA and protein synthesis, in most cases. Some of these pathways are unique targets for therapeutic manipulations in disease state. This chapter focuses on five families of cytokine receptors, which constitute immunoglobulin superfamily receptors, class I cytokine receptor family (hematopoietin receptor family), class II cytokine receptor family (interferon receptor family), TNF receptor family, and chemokine receptor family. Furthermore, cytokine receptor-associated transcription factors are discussed. Lastly, JAK-STAT signaling pathway, inhibitors of Janus kinases, mitogen-activated protein kinases, mitogen-activated protein kinase inhibitors, protein inhibitors of activated STATs (PIAS), and suppressors of cytokine signaling (SOCS) are described. The inhibitors of Janus kinases, MAPK, and STAT5-associated ligands are clinically used to treat a variety of diseases.

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Bibliography

  • Akira S (2003) Toll-like receptor signaling. J Biol Chem 278:38105–38108

    Article  CAS  PubMed  Google Scholar 

  • Alexander WS, Hilton DJ (2004) The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Ann Rev Immunol 22:503–529

    Article  CAS  Google Scholar 

  • Bazan JF (1990) Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci U S A 87:6934–6938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharya S, Eckner R, Grossman S, Oldread E et al (1996) Cooperation of Stat2 and p300/CBP in signaling induced by interferon-alpha. Nature 383:344–347

    Article  CAS  PubMed  Google Scholar 

  • Bonni A, Brunet A, West AE, Datta SR et al (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and –independent mechanisms. Science 286:1358–1362

    Article  CAS  PubMed  Google Scholar 

  • Bradley JR, Prober JS (2001) Tumor necrosis factor receptor associated factors (TRAFs). Oncogene 20:6482–6491

    Article  CAS  PubMed  Google Scholar 

  • Chadee DN, Yuasa T, Kyriakis JM (2002) Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. Mol Cell Biol 22:737–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang L, Karin M (2001) Mammalian MAP kinase signaling cascades. Nature 410:37–40

    Article  CAS  PubMed  Google Scholar 

  • Chang F, Steelman LS, Lee JT, Shelton JG et al (2003) Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokines to transcription factors: potential targeting for therapeutic intervention. Leukemia 17:1263–1293

    Article  CAS  PubMed  Google Scholar 

  • Chen G, Goeddel DV (2002) TNF-R1 signaling: a beautiful pathway. Sciences 296:1634–1635

    Article  CAS  Google Scholar 

  • Chen W, Hershey GKK (2007) Signal transducer and activator of transcription signals in allergic disease. J Allergy Clin Immunol 119:529–541

    Article  CAS  PubMed  Google Scholar 

  • Chen YR, Tan TH (1999) Mammalian c-jun n-terminal kinase pathway and ste20-related kinases. Gene Ther Mol Biol 4:83–98

    Google Scholar 

  • Cosman D, Lyman SD, Idzerda RL, Beckmann MP (1990) A new cytokine receptor superfamily. Trends Biochem Sci 15:265–270

    Article  CAS  PubMed  Google Scholar 

  • D’Andrea AD (1994) Cytokine receptors in congenital hematopoietic disease. NEJM 330:839–846

    Article  PubMed  Google Scholar 

  • Dai X, Chen Y, Di L, Podd A et al (2007) STAT5 is essential for early B cell development but not for B cell maturation and function. J Immunol 179:1068–1079

    Article  CAS  PubMed  Google Scholar 

  • Demetri GD, Mehren MV, Blanke CD, Van den Abbeele AD (2002) Efficacy and safety of Imatinib Mesylate in advanced gastrointestinal stromal tumors. N Eng J Med 347:472–480

    Article  CAS  Google Scholar 

  • deWeerd NA, Samarajiwa SA, Hertzog PJ (2007) Type 1 interferon receptors: biochemistry and biological functions. J Biol Chem 282:20053–20057

    Article  CAS  Google Scholar 

  • Druker BJ, Tamura S, Buchdunger E, Ohno S et al (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561–566

    Article  CAS  PubMed  Google Scholar 

  • Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC (2003) Cloning of new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. Biochem J 370:391–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egan PJ, Lawlor KE, Alexander PS, Wicks IP (2003) Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Invest 111:915–924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elkasmi KC, Holst J, Coffre M, Mielke C et al (2006) General nature of the STAT3-activated anti-inflammatory response. J Immunol 177:7880–7888

    Article  CAS  Google Scholar 

  • Escudier B, Eisen T, Stadler WM, Szczylik C (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  CAS  PubMed  Google Scholar 

  • Gadina M, Hilton D, Johnston JA, Morinobu A et al (2001) Signaling by type 1 and type II receptors: ten years after. Curr Opin Immunol 13:363–373

    Article  CAS  PubMed  Google Scholar 

  • Gauthier A (2013) Role of sorafenib in the treatment of advanced hepatocellular carcinoma: an update. Hepatol Res 43:147–154

    Article  CAS  PubMed  Google Scholar 

  • Geijsen N, Koenderman L, Coffer PJ (2001) Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family. Cytokine Growth Factor Rev 12:19–25

    Article  CAS  PubMed  Google Scholar 

  • Ghoreschi K, Jesson MI, Li X, Lee JL et al (2011) Modulation of innate and adaptive immune response by tofacitinib (CP-690, 550). J Immunol 186:4234–4243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldman JM, Melo JV (2003) Chronic myeloid leukemia – advances in biology and new approaches to treatment. N Engl J Med 349:1451–1464

    Article  CAS  PubMed  Google Scholar 

  • Gounder MM, Lefkowitz RA, Keohan ML, D’Adamo DR et al (2011) Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res: Off J Am Assoc Cancer Res 17:4082–4090

    Article  CAS  Google Scholar 

  • Grimley PM, Dong F, Rui H (1999) Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation. Cytokine Growth Factor Rev 10:131–157

    Article  CAS  PubMed  Google Scholar 

  • Haan C, Kreis S, Margue C, Behrmann I (2006) JAKs and Cytokine receptors – an intimate relationship. Biochem Pharmacol 72:1538–1546

    Article  CAS  PubMed  Google Scholar 

  • Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H et al (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366:787–798

    Article  CAS  PubMed  Google Scholar 

  • Harrison C, Mesa R, Ross D, Mead A et al (2013) Practical management of patients with myelofibrosis receiving ruxolitinib. Expert Rev Hematol 6:511–523

    Article  CAS  PubMed  Google Scholar 

  • Hazzalin CA, Mahadevan LC (2002) MAPK-regulated transcription: a continuously variable gene switch? Nat Rev Mol Cell Biol 3:30–40

    Article  CAS  PubMed  Google Scholar 

  • He YW, Adkins B, Furse RK, Malek TR (1995) Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor. J Immunol 154:1596–1605

    CAS  PubMed  Google Scholar 

  • Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L (1998) Interleukin-6 type cytokine signaling through the gp130/JAK/STAT pathway. Biochem J 334:297–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hershey GK (2003) IL-13 receptors and signaling pathways: an evolving web. J Allergy Clin Immunol 111:677–690

    Article  CAS  PubMed  Google Scholar 

  • Hescot S, Vignaux O, Goldwasser F (2013) Pancreatic atrophy- a new late toxic effect of sorafenib. N Eng J Med 369:1475–1476

    Article  CAS  Google Scholar 

  • http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231409.htm

  • Ihle JN (1995) Cytokine receptor signaling. Nature 377:591–594

    Article  CAS  PubMed  Google Scholar 

  • Ihle JN, Witthum BA, Quelle FW, Yamamoto K et al (1995) Signaling through the hematopoietic cytokine receptors. Ann Rev Immunol 13:369–398

    Article  CAS  Google Scholar 

  • Ivashkiv LB, Tassiulas I (2003) Can SOCS make arthritis better? J Clin Invest 111:795–797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kantarajian H, Giles F, Wunderle L, Bhalla K (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 354:2542–2551

    Article  Google Scholar 

  • Kato Y, Kravchenko VV, Tapping RI, Han J et al (1997) BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J 16:7054–7066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keating GM, Santoro A (2009) Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs 69:223–240

    Article  CAS  PubMed  Google Scholar 

  • Kiefer F, Tibbles LA, Anafi M, Janssen A et al (1996) HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. EMBO J 16:7013–7025

    Google Scholar 

  • Kondo M, Takeshita T, Ishii N, Nakamura M et al (1993) Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science 262:1874–1877

    Article  CAS  PubMed  Google Scholar 

  • Koziczak-Holbro M, Joyce C, Gluk A, Kinzel B et al (2007) IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor-7 mediated signaling and gene expression. J Biol Chem 282:13552–13560

    Article  CAS  PubMed  Google Scholar 

  • Krebs DL, Hilton DJ (2001) SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19:378–387

    Article  CAS  PubMed  Google Scholar 

  • Kremer JM, Bloom BJ, Breedveld FC, Coombs JH et al (2009) The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase II trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 60:1895–1905

    Article  CAS  PubMed  Google Scholar 

  • Kubo M, Hanada T, Yoshimura A (2003) Suppressors of cytokine signaling and immunity. Nat Immunol 4:1169–1176

    Article  CAS  PubMed  Google Scholar 

  • Lee EB, Fleischmann R, Hall S, Wilkinson B (2014) Tofacitinib versus methotrexate in rheumatoid arthritis. N Eng J Med 370:2377–2386

    Article  CAS  Google Scholar 

  • Levy DE, Lee C (2003) What does STAT3 do? J Clin Invest 109:1143–1148

    Article  Google Scholar 

  • Li Y, Shen BF, Karanes C, Sensenbrenner L, Chen B (1995) Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e). J Immunol 155:2165–2174

    CAS  PubMed  Google Scholar 

  • Li X, Leung S, Qureshi S, Darnell JE et al (1996) Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha. J Biol Chem 271:5790–5794

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390

    Article  CAS  PubMed  Google Scholar 

  • Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

    Article  CAS  PubMed  Google Scholar 

  • Lynch RA, Etchin J, Battle TE, Frank DA (2007) A small-molecule enhancer of signal transducer and activator of transcription 1 transcriptional activity accentuates the antiproliferative effects of IFN-γ in human cancer cells. Cancer Res 67:1254–1261

    Article  CAS  PubMed  Google Scholar 

  • Mandel M, Powers SE, Maienschein-Cline M, Bartom ET et al (2011) Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. Nat Immunol 12:1212–1220

    Article  CAS  Google Scholar 

  • Manley PW, Drueckes P, Fendrich G, Furet P et al (2010) Extended kinase profile and properties of the protein kinase inhibitor nilotinib. Biochim Biophys Acta 1804:445–453

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Moczygemba M, Huston DP (2003) Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF. J All Clin Immunol 112:653–665

    Article  CAS  Google Scholar 

  • Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC (1997) Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3. J Biol Chem 272:20070–20076

    Article  CAS  PubMed  Google Scholar 

  • Mesa RA (2010) Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis. Drugs: Invest Drugs J 13:394–403

    CAS  Google Scholar 

  • Miyajima A, Kitamura T, Harda N, Yokota T et al (1992) Cytokine receptors and signal transduction. Ann Rev Immunol 10:295–331

    Article  CAS  Google Scholar 

  • Moore KW, de-Waal R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Ann Rev Immunol 19:683–765

    Article  CAS  Google Scholar 

  • Murdoch C, Finn A (2000) Chemokine receptors and their role in inflammation and infectious diseases. Blood 95:3032–3043

    CAS  PubMed  Google Scholar 

  • Murphy PM (2002) International union of pharmacology. XXX. Update on chemokine receptor nomenclature. Pharmacol Rev 54:227–229

    Article  CAS  PubMed  Google Scholar 

  • Murray PJ (2007) The JAK-STAT signaling pathway: input and output integration. J Immunol 178:2623–2629

    Article  CAS  PubMed  Google Scholar 

  • Nguyen V-P, Saleh Abu ZM, Arch AE, Yan H (2002) Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling. J Biol Chem 277:9713–9721

    Article  CAS  PubMed  Google Scholar 

  • Nosaka T, Kawashima T, Misawa K, Ikuta K (1999) STAT5 as a molecular regulator of proliferation, differentiation, and apoptosis in hematopoietic cells. EMBO J 18:4754–4765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Neill LA (2002) Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily. Curr Top Microbiol Immunol 270:47–61

    PubMed  Google Scholar 

  • O’Sullivan LA, Liongue C, Lewis RS, Stephenson SE et al (2007) Cytokine receptor signaling through the JAK-stat-socs pathway in disease. Mol Immunol 44:2497–2506

    Article  PubMed  CAS  Google Scholar 

  • Ogata N, Kouro T, Yamada A, Koike M et al (1998) JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and beta c subunit, respectively, and are activated upon IL-5 stimulation. Blood 91:2264–2271

    CAS  PubMed  Google Scholar 

  • Olosz F, Malek TR (2002) Structural basis for binding multiple ligands by the common cytokine receptor gamma-chain. J Biol Chem 277:12047–12055

    Article  CAS  PubMed  Google Scholar 

  • Pawlik TM, Reyes DK, Cosgrove D, Kamel IR (2011) Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 29:3960–3967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson G, English JM, White MA, Cobb MH (2001a) ERK5 and ERK2 cooperate to regulate NF-kappa B and cell transformation. J Biol Chem 276:7927–7931

    Article  CAS  PubMed  Google Scholar 

  • Pearson G, Robinson F, Gibson TB, Xu BE et al (2001b) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153–183

    CAS  PubMed  Google Scholar 

  • Pestka S, Krause CD, Sarkar D, Walter MR (2004) Interleukin-10 and related cytokines and receptors. Ann Rev Immunol 22:929–979

    Article  CAS  Google Scholar 

  • Quelle FW, Sato N, Witthuhn BA, Inhorn RC et al (1994) JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol Cell Biol 14:4335–4341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radtke S, Haan S, Jorissen A, Hermanns HM et al (2005) The JAK1 SH2 domain does not fulfill a classical SH2 function in JAK/STAT signaling but plays a role for receptor interaction and up-regulation of receptor surface expression. J Biol Chem 280:25760–25768

    Article  CAS  PubMed  Google Scholar 

  • Ramana CV, Gil MP, Schreiber RD, Stark GR (2002) STAT-1-dependent and – independent pathways in IFN-γ-dependent signaling. Trends Immunol 23:96–101

    Article  CAS  PubMed  Google Scholar 

  • Ransohoff RM (1998) Cellular responses to interferons and other cytokines: the JAK-STAT paradigm. NEJM 338:616–168

    Article  CAS  PubMed  Google Scholar 

  • Rawlings JS, Rosler KM, Harrison DA (2004) The JAK/STAT signaling pathway. J Cell Sci 117:1281–1283

    Article  CAS  PubMed  Google Scholar 

  • Regis G, Conti L, Boselli D, Novelli F (2006) IFN gamma R2 trafficking tunes IFN gamma-STAT1 signaling in T lymphocytes. Trends Immunol 27:96–101

    Article  CAS  PubMed  Google Scholar 

  • Renauld JC (2003) Class II cytokine receptors and their ligands, key antiviral and inflammatory modulators. Nat Rev Immunol 3:667–676

    Article  CAS  PubMed  Google Scholar 

  • Rincon M, Pedraza-Alva G (2003) JNK and P38 MAP kinases in CD4+ and CD8+ T cells. Immunol Rev 192:131–142

    Article  CAS  PubMed  Google Scholar 

  • Roberts AW, Robb L, Rakar S, Hartley L et al (2001) Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. PNAS 98:9324–9329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saglio GS, Kim D-W, Issaragrisil S, le Coutre P (2010) Nilotinib versus Imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362:2251–2259

    Article  CAS  PubMed  Google Scholar 

  • Sato N, Sakamaki K, Terada N, Arai K, Miyajima A (1993) Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling. EMBO J 12:4181–4189

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt C, Peng G, Li Z, Sclabas GM et al (2003) Mechanisms of proinflammatory cytokine-induced biphasic NF-KB activation. Mol Cell 12:1287–1300

    Article  CAS  PubMed  Google Scholar 

  • Schroder K, Hertzog PJ, Ravasi T, Hume DA (2003) Interferon-γ, an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189

    Article  PubMed  CAS  Google Scholar 

  • Sharrocks AD (2006) PIAS proteins and transcriptional regulation – more than just SUMOE3 ligases. Genes Dev 20:754–758

    Article  CAS  PubMed  Google Scholar 

  • Shelburne CP, McCoy ME, Piekorz R, Sexl VV et al (2002) STAT5: an essential regulatory of mast cell biology. Mol Immunol 38:1187–1191

    Article  CAS  PubMed  Google Scholar 

  • Shetty K, Dash C, Laurin J (2014) Use of adjuvant Sorafenib in liver transplant recipients with high risk hepatocellular carcinoma. J Transplant 913634:5

    Google Scholar 

  • Shuai K (2006) Regulation of cytokine signaling pathways by PIAs proteins. Cell Res 16:196–202

    Article  CAS  PubMed  Google Scholar 

  • Shuai K, Liu B (2003) Regulation of JAK-STAT signaling in the immune system. Nat Rev Immunol 3:900–911

    Article  CAS  PubMed  Google Scholar 

  • Shuai K, Halpern J, ten Hoeve J, Rao X et al (1996) Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 13:247–254

    CAS  PubMed  Google Scholar 

  • Sims JE (2002) IL-1 and Il-18 receptors, and their extended family. Curr Opin Immunol 14:117–122

    Article  CAS  PubMed  Google Scholar 

  • Stephanou A, Latchman DS (2005) Opposing actions of STAT-1 and STAT-3. Growth Factors 23:177–182

    Article  CAS  PubMed  Google Scholar 

  • Stomski FC, Woodcock JM, Zacharakis B, Bagley CJ et al (1998) Identification of a Cys motif in the common beta chain of the interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 receptors essential for disulfide-linked receptor heterodimerization and activation of all three receptors. J Biol Chem 273:1192–1199

    Article  CAS  PubMed  Google Scholar 

  • Symons A, Beinke S, Ley SC (2006) MAP kinase kinase kinases and innate immunity. Trends Immunol 27:40–48

    Article  CAS  PubMed  Google Scholar 

  • Takaki S, Kanazawa H, Shiiba M, Takatsu K (1994) A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction. Mol Cell Biol 14:7404–7413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takaoka A, Hayakawa S, Yanai H, Stoiber D et al (2003) Integration of interferon-alpha/beta signaling to p53 responses in tumour suppression and antiviral defence. Nature 424:516–523

    Article  CAS  PubMed  Google Scholar 

  • Talpaz M, Shah NP, Kantarijian H, Donato N (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354:2531–254

    Article  CAS  PubMed  Google Scholar 

  • Tan SH, Nevalainen MT (2008) Signal transducer and activator of transcription 5A/B in prostate and breast cancers. Endocr Relat Cancer 15:367–390

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi T, Takaoka A (2002) The interferon-alpha/beta system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. Curr Opin Immunol 14:111–116

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi T, Ogasawara K, Takaoka A, Tanaka N (2001) IRS family of transcription factors as regulators of host defense. Ann Rev Immunol 19:623–655

    Article  CAS  Google Scholar 

  • Tavernier J, Devos R, Cornelis S, Tuypens T et al (1991) A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell 66:1175–1184

    Article  CAS  PubMed  Google Scholar 

  • Tefferi A (2012) Challenges facing JAK inhibitor therapy for myeloproliferative neoplasms. N Engl J Med 366:844–846

    Article  CAS  PubMed  Google Scholar 

  • Torii S, Nakayama K, Yamamoto T, Nishida E (2004) Regulatory mechanisms and function of ERK MAP kinases. J Biochem 136:557–561

    Article  CAS  PubMed  Google Scholar 

  • Uddin S, Chamdin A, Platanias LC (1995) Interaction of the transcriptional activator Stat-2 with the type I interferon receptor. J Biol Chem 270:24627–24630

    Article  CAS  PubMed  Google Scholar 

  • Van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB et al (2012) Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Eng J Med 367:508–519

    Article  CAS  Google Scholar 

  • Verstovsek S, Mesa RA, Gotlib J, Levy RS et al (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366:799–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wajant H, Henkler F, Scheurich P (2001) The TNF receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal 13:389–400

    Article  CAS  PubMed  Google Scholar 

  • Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10:45–65

    Article  CAS  PubMed  Google Scholar 

  • Waldmann T, Tagaya Y, Bamford R (1998) Interleukin 2, interleukin 15 and their receptors. Int Rev Immunol 16:205–226

    Article  CAS  PubMed  Google Scholar 

  • Watford WT, Hissong BD, Kannu JH, Muul L, O’Shea JJ (2004) Signaling by IL-12 and IL-23 and the immunoregulatory role of STAT4. Immunol Rev 202:139–156

    Article  CAS  PubMed  Google Scholar 

  • Weston CR, Lambright DG, Davis RJ (2002) Signal transduction. MAP kinase signaling specificity. Science 296:2345–2347

    Article  CAS  PubMed  Google Scholar 

  • Wilhelm SM, Adnane L, Newell P, Villanueva A et al (2008) Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 7:3129–3140

    Article  CAS  PubMed  Google Scholar 

  • Wong PKK, Egan PJ, Croker BA, Donnell KO et al (2004) SOCS3 negatively regulates innate and adaptive immune mechanism in acute IL-1-dependent inflammatory arthritis. J Clin Invest 116:1571–1581

    Article  CAS  Google Scholar 

  • Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W et al (2001) A soluble class II cytokine receptor, IL-22RA2 is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci U S A 98:9511–9516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeh TC, Pellegrini S (1999) The Janus Kinase family of protein tyrosine kinase and their ole in signaling. Cell Mol Life Sic 55:1523–1534

    Article  CAS  Google Scholar 

  • Yu Q, Thieu VT, Kaplan MH (2007) STAT4 limits DNA methyl transferase recruitment and DNA methylation of the IL-18R1 gene during TH1 differentiation. EMBO J 26:2052–2060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Pharmacy Sciences, Creighton University, Omaha, Nebraska, USA

    Manzoor M. Khan

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Khan, M.M. (2016). Cytokine Receptors and Signaling. In: Immunopharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-30273-7_3

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