Skip to main content

Cytokine Receptors and Signaling

  • Chapter
  • First Online:
Immunopharmacology
  • 846 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Bibliography

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

    Article  PubMed  CAS  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 Nat Acad Sci. USA. 87:6934–6938.

    Article  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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.

    CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chen G, Goeddel DV. 2002. TNF-R1 signaling: A beautiful pathway. Science. 296:1634–1635.

    Article  PubMed  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  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  PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  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 

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

    CAS  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.

    CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Haan C, Kreis S, Margue C, Behrmann I. 2006. JAKs and cytokine receptors – An intimate relationship. Biochem Pharmacol. 72:1538–1546.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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.

    PubMed  CAS  Google Scholar 

  • Hershey GK. 2003. IL-13 receptors and signaling pathways: An evolving web. J All Clin Immunol. 111:677–690.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  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 Inv. 111:795–797.

    CAS  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  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Levy DE, Lee C. 2003. What does STAT3 do? J Clin Inv. 109:1143–1148.

    Google Scholar 

  • Li Y, shen BF, Karanes C, Sensenbrenner L, Chen B. 1995. Association between Lyn protein tyrosine kinase (p53/56 lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) recepto9rs in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e). J Immunol. 155:2165–2174.

    Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  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 

  • 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.

    Google Scholar 

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

    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 betac subunit, respectively, and are activated upon IL-5 stimulation. Blood. 91:2264–2271.

    PubMed  CAS  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  PubMed  CAS  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.

    Article  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  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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.

    PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  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.

    PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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.

    PubMed  CAS  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  PubMed  CAS  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 

  • 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  PubMed  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  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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 Inv. 116:1571–1581.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manzoor M. Khan Ph.D. .

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Khan, M.M. (2008). Cytokine Receptors and Signaling. In: Immunopharmacology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-77976-8_3

Download citation

Publish with us

Policies and ethics