Abstract
Cytokine receptors initiate intracellular signaling that regulate a diverse range of biological and medically important functions including metabolism control, neural stem cell activation, inflammatory responses, bone development, as well as blood cell and immune cell development and growth. The unifying feature of these receptors is their ability to activate the JAK-STAT pathway; however, they are grouped into two structurally related classes, known as class I and class II. Class I cytokine receptors have over 30 members including receptors for erythropoietin (EPO), prolactin (PRL), growth hormone (GH), thrombopoietin (TPO), leptin, (LEP), granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), interleukin-3 (IL-3), IL-5, IL-6, and IL-7. The class II cytokine receptor family includes the interferon receptors, IL-10 receptor, and number of more recently discovered cytokine receptors for IL-19, IL-20, IL-22, IL-24, IL-26, and IL-29. This chapter will review the structure, activation mechanism, and signaling of cytokine receptors.
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References
Abdel-Meguid SS, Shieh HS, Smith WW, Dayringer HE, Violand BN, Bentle LA. Three-dimensional structure of a genetically engineered variant of porcine growth hormone. Proc Natl Acad Sci USA. 1987;84(18):6434–7.
Acosta JJ, Munoz RM, Gonzalez L, Subtil-Rodriguez A, Dominguez-Caceres MA, Garcia-Martinez JM, et al. Src mediates prolactin-dependent proliferation of T47D and MCF7 cells via the activation of focal adhesion kinase/Erk1/2 and phosphatidylinositol 3-kinase pathways. Mol Endocrinol. 2003;17(11):2268–82.
Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol. 2004;22:503–29.
Babon JJ, Lucet IS, Murphy JM, Nicola NA, Varghese LN. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462(1):1–13.
Bagley CJ, Woodcock JM, Stomski FC, Lopez AF. The structural and functional basis of cytokine receptor activation: lessons from the common beta subunit of the granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 receptors. Blood. 1997;89(5):1471–82.
Baker SJ, Rane SG, Reddy EP. Hematopoietic cytokine receptor signaling. Oncogene. 2007;26(47):6724–37.
Barclay JL, Anderson ST, Waters MJ, Curlewis JD. SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL. Int J Cancer. 2009;124(8):1756–66.
Barnard R, Quirk P, Waters MJ. Characterization of the growth hormone-binding protein of human serum using a panel of monoclonal antibodies. J Endocrinol. 1989;123(2):327–32.
Baumann G. Growth hormone binding protein. The soluble growth hormone receptor. Minerva Endocrinol. 2002;27(4):265–76.
Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA. 1990;87(18):6934–8.
Bogorad RL, Courtillot C, Mestayer C, Bernichtein S, Harutyunyan L, Jomain JB, et al. Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. Proc Natl Acad Sci USA. 2008;105(38):14533–8.
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225–68.
Bompard G, Martin M, Roy C, Vignon F, Freiss G. Membrane targeting of protein tyrosine phosphatase PTPL1 through its FERM domain via binding to phosphatidylinositol 4,5-biphosphate. J Cell Sci. 2003;116(Pt 12):2519–30.
Boulanger MJ, Chow DC, Brevnova EE, Garcia KC. Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science. 2003;300(5628):2101–4.
Braunstein J, Brutsaert S, Olson R, Schindler C. STATs dimerize in the absence of phosphorylation. J Biol Chem. 2003;278(36):34133–40.
Brooks AJ, Waters MJ. The growth hormone receptor: mechanism of activation and clinical implications. Nat Rev Endocrinol. 2010;6(9):515–25.
Brooks AJ, Waters MJ. Rewriting the mechanism of JAK2 activation. Cell Cycle. 2015;14(3):285–6.
Brooks AJ, Wooh JW, Tunny KA, Waters MJ. Growth hormone receptor; mechanism of action. Int J Biochem Cell Biol. 2008;40(10):1984–9.
Brooks AJ, Dai W, O’Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science. 2014;344(6185):1249783.
Broughton SE, Dhagat U, Hercus TR, Nero TL, Grimbaldeston MA, Bonder CS, et al. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunol Rev. 2012;250(1):277–302.
Broughton SE, Hercus TR, Hardy MP, McClure BJ, Nero TL, Dottore M, et al. Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody. Cell Rep. 2014;8(2):410–9.
Broughton SE, Nero TL, Dhagat U, Kan WL, Hercus TR, Tvorogov D, et al. The beta c receptor family – structural insights and their functional implications. Cytokine. 2015;74(2):247–58.
Broughton SE, Hercus TR, Nero TL, Dottore M, McClure BJ, Dhagat U, et al. Conformational changes in the GM-CSF receptor suggest a molecular mechanism for affinity conversion and receptor signaling. Structure. 2016;24(8):1271–81.
Broutin I, Jomain JB, Tallet E, van Agthoven J, Raynal B, Hoos S, et al. Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2. J Biol Chem. 2010;285(11):8422–33.
Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, et al. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol. 2005;12(9):814–21.
Bugge K, Lindorff-Larsen K, Kragelund BB. Understanding single-pass transmembrane receptor signaling from a structural viewpoint – what are we missing? FEBS J. 2016a. doi:10.1111/febs.13793.
Bugge K, Papaleo E, Haxholm GW, Hopper JT, Robinson CV, Olsen JG, et al. A combined computational and structural model of the full-length human prolactin receptor. Nat Commun. 2016b;7:11578.
Carr PD, Gustin SE, Church AP, Murphy JM, Ford SC, Mann DA, et al. Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration. Cell. 2001;104(2):291–300.
Chen C, Brinkworth R, Waters MJ. The role of receptor dimerization domain residues in growth hormone signaling. J Biol Chem. 1997;272(8):5133–40.
Chen M, Cheng A, Candotti F, Zhou YJ, Hymel A, Fasth A, et al. Complex effects of naturally occurring mutations in the JAK3 pseudokinase domain: evidence for interactions between the kinase and pseudokinase domains. Mol Cell Biol. 2000;20(3):947–56.
Chhabra Y, Waters MJ, Brooks AJ. Role of the growth hormone–IGF-1 axis in cancer. Expert Rev Endocrinol Metab. 2011;6:71–84.
Chin H, Arai A, Wakao H, Kamiyama R, Miyasaka N, Miura O. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway. Blood. 1998;91(10):3734–45.
Clackson T, Ultsch MH, Wells JA, de Vos AM. Structural and functional analysis of the 1:1 growth hormone:receptor complex reveals the molecular basis for receptor affinity. J Mol Biol. 1998;277(5):1111–28.
Clevenger CV. Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland? Breast Cancer Res. 2003;5(4):181–7.
Clevenger CV, Medaglia MV. The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes. Mol Endocrinol. 1994;8(6):674–81.
Clevenger CV, Gadd SL, Zheng J. New mechanisms for PRLr action in breast cancer. Trends Endocrinol Metab. 2009;20(5):223–9.
Conway-Campbell BL, Wooh JW, Brooks AJ, Gordon D, Brown RJ, Lichanska AM, et al. Nuclear targeting of the growth hormone receptor results in dysregulation of cell proliferation and tumorigenesis. Proc Natl Acad Sci U S A. 2007;104(33):13331–6.
Conway-Campbell BL, Brooks AJ, Robinson PJ, Perani M, Waters MJ. The extracellular domain of the growth hormone receptor interacts with coactivator activator to promote cell proliferation. Mol Endocrinol. 2008;22(9):2190–202.
Cunningham BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science. 1991;254(5033):821–5.
Dagil R, Knudsen MJ, Olsen JG, O’Shea C, Franzmann M, Goffin V, et al. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor. Structure. 2012;20(2):270–82.
Dahl C, Hoffmann HJ, Saito H, Schiotz PO. Human mast cells express receptors for IL-3, IL-5 and GM-CSF; a partial map of receptors on human mast cells cultured in vitro. Allergy. 2004;59(10):1087–96.
Darnell Jr JE. STATs and gene regulation. Science. 1997;277(5332):1630–5.
Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, et al. Attributes of short linear motifs. Mol BioSyst. 2012;8(1):268–81.
de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992;255(5042):306–12.
Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol. 2004;76(2):314–21.
Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, JS O, et al. Intrinsically disordered protein. J Mol Graph Model. 2001;19(1):26–59.
Dyson HJ, Wright PE. Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol. 2005;6(3):197–208.
Elkins PA, Christinger HW, Sandowski Y, Sakal E, Gertler A, de Vos AM, et al. Ternary complex between placental lactogen and the extracellular domain of the prolactin receptor. Nat Struct Biol. 2000;7(9):808–15.
Elson GC, Lelievre E, Guillet C, Chevalier S, Plun-Favreau H, Froger J, et al. CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat Neurosci. 2000;3(9):867–72.
Feng J, Mertz B. Novel phosphatidylinositol 4,5-bisphosphate binding sites on focal adhesion kinase. PLoS One. 2015;10(7):e0132833.
Ferrao R, Wallweber HJ, Ho H, Tam C, Franke Y, Quinn J, et al. The structural basis for class II cytokine receptor recognition by JAK1. Structure. 2016;24(6):897–905.
Finter NB. The naming of cats-and alpha-interferons. Lancet. 1996;348(9024):348–9.
Fox BA, Sheppard PO, O’Hara PJ. The role of genomic data in the discovery, annotation and evolutionary interpretation of the interferon-lambda family. PLoS One. 2009;4(3):e4933.
Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiol Rev. 2000;80(4):1523–631.
Fresno Vara JA, Carretero MV, Geronimo H, Ballmer-Hofer K, Martin-Perez J. Stimulation of c-Src by prolactin is independent of Jak2. Biochem J. 2000;345(Pt 1):17–24.
Fu YK, Arkins S, Fuh G, Cunningham BC, Wells JA, Fong S, et al. Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. J Clin Invest. 1992;89(2):451–7.
Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992;256(5064):1677–80.
Fuxreiter M. Fuzziness: linking regulation to protein dynamics. Mol BioSyst. 2012;8(1):168–77.
Fuxreiter M, Simon I, Friedrich P, Tompa P. Preformed structural elements feature in partner recognition by intrinsically unstructured proteins. J Mol Biol. 2004;338(5):1015–26.
Fuxreiter M, Tompa P, Simon I. Local structural disorder imparts plasticity on linear motifs. Bioinformatics. 2007;23(8):950–6.
Gery S, Cao Q, Gueller S, Xing H, Tefferi A, Koeffler HP. Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F. J Leukoc Biol. 2009;85(6):957–65.
Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273–87.
Ginsburg E, Vonderhaar BK. Prolactin synthesis and secretion by human breast cancer cells. Cancer Res. 1995;55(12):2591–5.
Girault JA, Labesse G, Mornon JP, Callebaut I. The N-termini of FAK and JAKs contain divergent band 4.1 domains. Trends Biochem Sci. 1999;24(2):54–7.
Gutschalk CM, Yanamandra AK, Linde N, Meides A, Depner S, Mueller MM. GM-CSF enhances tumor invasion by elevated MMP-2, −9, and −26 expression. Cancer Med. 2013;2(2):117–29.
Haan C, Kreis S, Margue C, Behrmann I. Jaks and cytokine receptors – an intimate relationship. Biochem Pharmacol. 2006;72(11):1538–46.
Hamada K, Shimizu T, Matsui T, Tsukita S, Hakoshima T. Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. EMBO J. 2000;19(17):4449–62.
Hammaren HM, Ungureanu D, Grisouard J, Skoda RC, Hubbard SR, Silvennoinen O. ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation. Proc Natl Acad Sci USA. 2015;112(15):4642–7.
Hansen G, Hercus TR, McClure BJ, Stomski FC, Dottore M, Powell J, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell. 2008a;134(3):496–507.
Hansen G, Hercus TR, Xu Y, Lopez AF, Parker MW, McKinstry WJ. Crystallization and preliminary X-ray diffraction analysis of the ternary human GM-CSF receptor complex. Acta Crystallogr Sect F: Struct Biol Cryst Commun. 2008b;64(Pt 8):711–4.
Haxholm GW, Nikolajsen LF, Olsen JG, Fredsted J, Larsen FH, Goffin V, et al. Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes. Biochem J. 2015;468(3):495–506.
Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998;334(Pt 2):297–314.
Hercus TR, Thomas D, Guthridge MA, Ekert PG, King-Scott J, Parker MW, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009;114(7):1289–98.
Hercus TR, Dhagat U, Kan WL, Broughton SE, Nero TL, Perugini M, et al. Signalling by the betac family of cytokines. Cytokine Growth Factor Rev. 2013;24(3):189–201.
Herington AC, Brooks AJ. Growth hormone-binding proteins. Ref Module Biomed Res. 2014; http://dx.doi.org/10.1016/B978-0-12-801238-3.04053-8.
Hilton DJ, Watowich SS, Murray PJ, Lodish HF. Increased cell surface expression and enhanced folding in the endoplasmic reticulum of a mutant erythropoietin receptor. Proc Natl Acad Sci USA. 1995;92(1):190–4.
Horseman ND, Gregerson KA. Prolactin actions. J Mol Endocrinol. 2014;52(1):R95–106.
Huyton T, Zhang JG, Luo CS, Lou MZ, Hilton DJ, Nicola NA, et al. An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor. Proc Natl Acad Sci USA. 2007;104(31):12737–42.
Ingley E. Functions of the Lyn tyrosine kinase in health and disease. Cell Commun Signal. 2012;10(1):21.
Iyer J, Reich NC. Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain. FASEB J. 2008;22(2):391–400.
Jenkins BJ, Roberts AW, Greenhill CJ, Najdovska M, Lundgren-May T, Robb L, et al. Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis. Blood. 2007;109(6):2380–8.
Jomain JB, Tallet E, Broutin I, Hoos S, van Agthoven J, Ducruix A, et al. Structural and thermodynamic bases for the design of pure prolactin receptor antagonists: X-ray structure of Del1-9-G129R-hPRL. J Biol Chem. 2007;282(45):33118–31.
Keeler C, Hodsdon ME, Dannies PS. Is there structural specificity in the reversible protein aggregates that are stored in secretory granules? J Mol Neurosci. 2004;22(1–2):43–9.
Kim MJ, Park SH, Opella SJ, Marsilje TH, Michellys PY, Seidel HM, et al. NMR structural studies of interactions of a small, nonpeptidyl tpo mimic with the thrombopoietin receptor extracellular juxtamembrane and transmembrane domains. J Biol Chem. 2007;282(19):14253–61.
Kobayashi N, Kono T, Hatakeyama M, Minami Y, Miyazaki T, Perlmutter RM, et al. Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. Proc Natl Acad Sci USA. 1993;90(9):4201–5.
Kossiakoff AA, De Vos AM. Structural basis for cytokine hormone-receptor recognition and receptor activation. Adv Protein Chem. 1998;52:67–108.
Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S. Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J. 1997;16(19):5894–903.
Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003;4(1):69–77.
Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev. 2004;202:67–83.
Lai SY, Xu W, Gaffen SL, Liu KD, Longmore GD, Greene WC, et al. The molecular role of the common gamma c subunit in signal transduction reveals functional asymmetry within multimeric cytokine receptor complexes. Proc Natl Acad Sci U S A. 1996;93(1):231–5.
Langer JA, Cutrone EC, Kotenko S. The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions. Cytokine Growth Factor Rev. 2004;15(1):33–48.
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–34.
Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, et al. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987;330(6148):537–43.
Levy DE, Darnell Jr JE. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651–62.
Li Q, Wong YL, Huang Q, Kang C. Structural insight into the transmembrane domain and the juxtamembrane region of the erythropoietin receptor in micelles. Biophys J. 2014;107(10):2325–36.
Li Q, Wong YL, Yueqi Lee M, Li Y, Kang C. Solution structure of the transmembrane domain of the mouse erythropoietin receptor in detergent micelles. Sci Rep. 2015;5:13586.
Lichanska AM, Waters MJ. New insights into growth hormone receptor function and clinical implications. Horm Res. 2008;69(3):138–45.
Linossi EM, Babon JJ, Hilton DJ, Nicholson SE. Suppression of cytokine signaling: the SOCS perspective. Cytokine Growth Factor Rev. 2013;24(3):241–8.
Liongue C, Ward AC. Evolution of class I cytokine receptors. BMC Evol Biol. 2007;7:120.
Liongue C, Sertori R, Ward AC. Evolution of cytokine receptor signaling. J Immunol. 2016;197(1):11–8.
Livnah O, Johnson DL, Stura EA, Farrell FX, Barbone FP, You Y, et al. An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation. Nat Struct Biol. 1998;5(11):993–1004.
Livnah O, Stura EA, Middleton SA, Johnson DL, Jolliffe LK, Wilson IA. Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Science. 1999;283(5404):987–90.
Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988;167(1):219–24.
Lupardus PJ, Skiniotis G, Rice AJ, Thomas C, Fischer S, Walz T, et al. Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Ralpha cytokine receptor complex, and the receptor-Jak1 holocomplex. Structure. 2011;19(1):45–55.
Masse GX, Corcuff E, Decaluwe H, Bommhardt U, Lantz O, Buer J, et al. gamma(c) cytokines provide multiple homeostatic signals to naive CD4(+) T cells. Eur J Immunol. 2007;37(9):2606–16.
Matadeen R, Hon WC, Heath JK, Jones EY, Fuller S. The dynamics of signal triggering in a gp130-receptor complex. Structure. 2007;15(4):441–8.
McElroy CA, Dohm JA, Walsh ST. Structural and biophysical studies of the human IL-7/IL-7Ralpha complex. Structure. 2009;17(1):54–65.
McElroy CA, Holland PJ, Zhao P, Lim JM, Wells L, Eisenstein E, et al. Structural reorganization of the interleukin-7 signaling complex. Proc Natl Acad Sci U S A. 2012;109(7):2503–8.
Miller SL, Antico G, Raghunath PN, Tomaszewski JE, Clevenger CV. Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells. Oncogene. 2007;26(32):4668–78.
Miyajima A, Hara T, Kitamura T. Common subunits of cytokine receptors and the functional redundancy of cytokines. Trends Biochem Sci. 1992;17(10):378–82.
Mohan A, Oldfield CJ, Radivojac P, Vacic V, Cortese MS, Dunker AK, et al. Analysis of molecular recognition features (MoRFs). J Mol Biol. 2006;362(5):1043–59.
Murphy JM, Ford SC, Wiedemann UM, Carr PD, Ollis DL, Young IG. A novel functional epitope formed by domains 1 and 4 of the human common beta-subunit is involved in receptor activation by granulocyte macrophage colony-stimulating factor and interleukin 5. J Biol Chem. 2003;278(12):10572–7.
Nebiker CA, Han J, Eppenberger-Castori S, Iezzi G, Hirt C, Amicarella F, et al. GM-CSF production by tumor cells is associated with improved survival in colorectal cancer. Clin Cancer Res. 2014;20(12):3094–106.
Neduva V, Linding R, Su-Angrand I, Stark A, de Masi F, Gibson TJ, et al. Systematic discovery of new recognition peptides mediating protein interaction networks. PLoS Biol. 2005;3(12):e405.
Nelson BH, Lord JD, Greenberg PD. A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells. Mol Cell Biol. 1996;16(1):309–17.
Nicola NA, Hilton DJ. General classes and functions of four-helix bundle cytokines. Adv Protein Chem. 1998;52:1–65.
Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993;73(1):147–57.
Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ. Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia. 2008;13(1):13–28.
Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev. 2010;19(115):46–54.
Olsen JG, Kragelund BB. Who climbs the tryptophan ladder? On the structure and function of the WSXWS motif in cytokine receptors and thrombospondin repeats. Cytokine Growth Factor Rev. 2014;25(3):337–41.
Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29:71–109.
Ozaki K, Leonard WJ. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem. 2002;277(33):29355–8.
Park MJ, Sheng R, Silkov A, Jung DJ, Wang ZG, Xin Y, et al. SH2 domains serve as lipid-binding modules for pTyr-signaling proteins. Mol Cell. 2016;62(1):7–20.
Patwardhan P, Resh MD. Myristoylation and membrane binding regulate c-Src stability and kinase activity. Mol Cell Biol. 2010;30(17):4094–107.
Perugini M, Brown AL, Salerno DG, Booker GW, Stojkoski C, Hercus TR, et al. Alternative modes of GM-CSF receptor activation revealed using activated mutants of the common beta-subunit. Blood. 2010;115(16):3346–53.
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol. 2004a;22:929–79.
Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunol Rev. 2004b;202:8–32.
Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol. 2004;172(4):2225–31.
Rane SG, Reddy EP. JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells. Oncogene. 1994;9(8):2415–23.
Rawat A, Nagaraj R. Determinants of membrane association in the SH4 domain of Fyn: roles of N-terminus myristoylation and side-chain thioacylation. Biochim Biophys Acta. 2010;1798(10):1854–63.
Rawat A, Harishchandran A, Nagaraj R. Fatty acyl chain-dependent but charge-independent association of the SH4 domain of Lck with lipid membranes. J Biosci. 2013;38(1):63–71.
Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117(Pt 8):1281–3.
Renauld JC. Class II, cytokine receptors and their ligands: key antiviral and inflammatory modulators. Nat Rev Immunol. 2003;3(8):667–76.
Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol. 2009;9(7):480–90.
Rowlinson SW, Yoshizato H, Barclay JL, Brooks AJ, Behncken SN, Kerr LM, et al. An agonist-induced conformational change in the growth hormone receptor determines the choice of signalling pathway. Nat Cell Biol. 2008;10(6):740–7.
Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L, et al. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J Immunol. 2007;178(4):2229–40.
Sabat R. IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010;21(5):315–24.
Saharinen P, Silvennoinen O. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J Biol Chem. 2002;277(49):47954–63.
Saharinen P, Vihinen M, Silvennoinen O. Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain. Mol Biol Cell. 2003;14(4):1448–59.
Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14(4):778–809. table of contents.
Sanz Sanz A, Niranjan Y, Hammaren H, Ungureanu D, Ruijtenbeek R, Touw IP, et al. The JH2 domain and SH2-JH2 linker regulate JAK2 activity: a detailed kinetic analysis of wild type and V617F mutant kinase domains. Biochim Biophys Acta. 2014;1844(10):1835–41.
Sato N, Miyajima A. Multimeric cytokine receptors: common versus specific functions. Curr Opin Cell Biol. 1994;6(2):174–9.
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011;1813(5):878–88.
Schuster B, Meinert W, Rose-John S, Kallen KJ. The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane. FEBS Lett. 2003;538(1–3):113–6.
Sheikh F, Baurin VV, Lewis-Antes A, Shah NK, Smirnov SV, Anantha S, et al. Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2. J Immunol. 2004;172(4):2006–10.
Sheng R, Jung DJ, Silkov A, Kim H, Singaram I, Wang ZG, et al. Lipids regulate Lck activity through their interactions with the Lck SH2 domain. J Biol Chem. 2016;291(34):17639–50.
Shuai K, Liu B. Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol. 2003;3(11):900–11.
Sigalov AB. Cells diversify transmembrane signaling through the controlled chaos of protein disorder. Self Nonself. 2011;2(2):75–9.
Silvennoinen O, Hubbard SR. Molecular insights into regulation of JAK2 in myeloproliferative neoplasms. Blood. 2015;125(22):3388–92.
Singleton KR, Kim J, Hinz TK, Marek LA, Casas-Selves M, Hatheway C, et al. A receptor tyrosine kinase network composed of fibroblast growth factor receptors, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, and hepatocyte growth factor receptor drives growth and survival of head and neck squamous carcinoma cell lines. Mol Pharmacol. 2013;83(4):882–93.
Skiniotis G, Boulanger MJ, Garcia KC, Walz T. Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor. Nat Struct Mol Biol. 2005;12(6):545–51.
Skiniotis G, Lupardus PJ, Martick M, Walz T, Garcia KC. Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex. Mol Cell. 2008;31(5):737–48.
Slavova-Azmanova NS, Kucera N, Louw A, Satiaputra J, Handoko A, Singer P, et al. Lyn kinase plays important roles in erythroid expansion, maturation and erythropoietin receptor signalling by regulating inhibitory signalling pathways that control survival. Biochem J. 2014;459(3):455–66.
Somers W, Ultsch M, De Vos AM, Kossiakoff AA. The X-ray structure of a growth hormone-prolactin receptor complex. Nature. 1994;372(6505):478–81.
Sprang SR, Bazan JF. Cytokine structural taxonomy and mechanisms of receptor engagement. Curr Opin Struct Biol. 1993;3(6):815–27.
Srivastava S, Matsuda M, Hou Z, Bailey JP, Kitazawa R, Herbst MP, et al. Receptor activator of NF-kappaB ligand induction via Jak2 and Stat5a in mammary epithelial cells. J Biol Chem. 2003;278(46):46171–8.
Stomski FC, Woodcock JM, Zacharakis B, Bagley CJ, Sun Q, Lopez AF. 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. 1998;273(2):1192–9.
Su S, Liu Q, Chen J, Chen J, Chen F, He C, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25(5):605–20.
Suzuki K, Nakajima H, Saito Y, Saito T, Leonard WJ, Iwamoto I. Janus kinase 3 (Jak3) is essential for common cytokine receptor gamma chain (gamma(c))-dependent signaling: comparative analysis of gamma(c), Jak3, and gamma(c) and Jak3 double-deficient mice. Int Immunol. 2000;12(2):123–32.
Svensson LA, Bondensgaard K, Norskov-Lauritsen L, Christensen L, Becker P, Andersen MD, et al. Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor. J Biol Chem. 2008;283(27):19085–94.
Tan D, Tan S, Zhang J, Tang P, Huang J, Zhou W, et al. Histone trimethylation of the p53 gene by expression of a constitutively active prolactin receptor in prostate cancer cells. Chin J Physiol. 2013;56(5):282–90.
Tantos A, Han KH, Tompa P. Intrinsic disorder in cell signaling and gene transcription. Mol Cell Endocrinol. 2012;348(2):457–65.
Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB. Solution structure of human prolactin. J Mol Biol. 2005;351(4):810–23.
Toms AV, Deshpande A, McNally R, Jeong Y, Rogers JM, Kim CU, et al. Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases. Nat Struct Mol Biol. 2013;20(10):1221–3.
Trinchieri G. Type I, interferon: friend or foe? J Exp Med. 2010;207(10):2053–63.
Tworoger SS, Eliassen AH, Zhang X, Qian J, Sluss PM, Rosner BA, et al. A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development. Cancer Res. 2013;73(15):4810–9.
Uchida H, Banba S, Wada M, Matsumoto K, Ikeda M, Naito N, et al. Analysis of binding properties between 20 kDa human growth hormone (hGH) and hGH receptor (hGHR): the binding affinity for hGHR extracellular domain and mode of receptor dimerization. J Mol Endocrinol. 1999;23(3):347–53.
Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, et al. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol. 2011;18(9):971–6.
Urdinguio RG, Fernandez AF, Moncada-Pazos A, Huidobro C, Rodriguez RM, Ferrero C, et al. Immune-dependent and independent antitumor activity of GM-CSF aberrantly expressed by mouse and human colorectal tumors. Cancer Res. 2013;73(1):395–405.
Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, et al. Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation. J Biol Chem. 2002;277(50):48220–6.
Vacic V, Oldfield CJ, Mohan A, Radivojac P, Cortese MS, Uversky VN, et al. Characterization of molecular recognition features, MoRFs, and their binding partners. J Proteome Res. 2007;6(6):2351–66.
van Agthoven J, Zhang C, Tallet E, Raynal B, Hoos S, Baron B, et al. Structural characterization of the stem-stem dimerization interface between prolactin receptor chains complexed with the natural hormone. J Mol Biol. 2010;404(1):112–26.
Wallweber HJ, Tam C, Franke Y, Starovasnik MA, Lupardus PJ. Structural basis of recognition of interferon-alpha receptor by tyrosine kinase 2. Nat Struct Mol Biol. 2014;21(5):443–8.
Walsh ST. Structural insights into the common gamma-chain family of cytokines and receptors from the interleukin-7 pathway. Immunol Rev. 2012;250(1):303–16.
Walsh ST, Sylvester JE, Kossiakoff AA. The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled. Proc Natl Acad Sci U S A. 2004;101(49):17078–83.
Walter MR, Cook WJ, Ealick SE, Nagabhushan TL, Trotta PP, Bugg CE. Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor. J Mol Biol. 1992;224(4):1075–85.
Wang M, Tan Z, Zhang R, Kotenko SV, Liang P. Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. J Biol Chem. 2002;277(9):7341–7.
Wang X, Lupardus P, Laporte SL, Garcia KC. Structural biology of shared cytokine receptors. Annu Rev Immunol. 2009;27:29–60.
Wang Y, Han G, Wang K, Liu G, Wang R, Xiao H, et al. Tumor-derived GM-CSF promotes inflammatory colon carcinogenesis via stimulating epithelial release of VEGF. Cancer Res. 2014;74(3):716–26.
Waters MJ, Brooks AJ. Growth hormone receptor: structure function relationships. Horm Res Paediatr. 2011;76(Suppl 1):12–6.
Waters MJ, Brooks AJ. JAK2 activation by growth hormone and other cytokines. Biochem J. 2015;466(1):1–11.
Watowich SS, Wu H, Socolovsky M, Klingmuller U, Constantinescu SN, Lodish HF. Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu Rev Cell Dev Biol. 1996;12:91–128.
Wells JA, de Vos AM. Hematopoietic receptor complexes. Annu Rev Biochem. 1996;65:609–34.
Wells JA, Kossiakoff AA. Cell biology. New tricks for an old dimer. Science. 2014;344(6185):703–4.
Wennbo H, Gebre-Medhin M, Gritli-Linde A, Ohlsson C, Isaksson OG, Tornell J. Activation of the prolactin receptor but not the growth hormone receptor is important for induction of mammary tumors in transgenic mice. J Clin Invest. 1997;100(11):2744–51.
Wilks AF, Harpur AG, Kurban RR, Ralph SJ, Zurcher G, Ziemiecki A. Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Mol Cell Biol. 1991;11(4):2057–65.
Wright PE, Dyson HJ. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol. 1999;293(2):321–31.
Wu W, Sun XH. Janus kinase 3: the controller and the controlled. Acta Biochim Biophys Sin Shanghai. 2012;44(3):187–96.
Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000;275(40):31335–9.
Xu Y, Kershaw NJ, Luo CS, Soo P, Pocock MJ, Czabotar PE, et al. Crystal structure of the entire ectodomain of gp130: insights into the molecular assembly of the tall cytokine receptor complexes. J Biol Chem. 2010;285(28):21214–8.
Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45(2):27–37.
Zhang C, Cherifi I, Nygaard M, Haxholm GW, Bogorad RL, Bernadet M, et al. Residue 146 regulates prolactin receptor folding, basal activity and ligand-responsiveness: potential implications in breast tumorigenesis. Mol Cell Endocrinol. 2015;401:173–88.
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Brooks, A.J., Dehkhoda, F., Kragelund, B.B. (2017). Cytokine Receptors. In: Belfiore, A., LeRoith, D. (eds) Principles of Endocrinology and Hormone Action. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-27318-1_8-2
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Cytokine Receptors- Published:
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DOI: https://doi.org/10.1007/978-3-319-27318-1_8-2
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Cytokine Receptors- Published:
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DOI: https://doi.org/10.1007/978-3-319-27318-1_8-1