The GM-CSF/IL-3/IL-5 cytokine receptor family: From ligand recognition to initiation of signaling

Immunological Reviews

Volumn 250, Issue 1, 2012, Pages 277-302

  Broughton, Sophie E ^a   Dhagat, Urmi ^a   Hercus, Timothy R ^b   Nero, Tracy L ^a   Grimbaldeston, Michele A ^b   Bonder, Claudine S ^b   Lopez, Angel F ^b   Parker, Michael W ^a,c  

^a ST VINCENT'S INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b CENTRE FOR CANCER BIOLOGY   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Crystal structures; cytokine; granulocyte macrophage colony stimulating factor; interleukin 3; interleukin 5; receptor signaling

Indexed keywords

ERYTHROPOIETIN; FC RECEPTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR ALPHA; HOMODIMER; INTERLEUKIN 3; INTERLEUKIN 3 RECEPTOR; INTERLEUKIN 5; INTERLEUKIN 5 RECEPTOR; INTERLEUKIN 5 RECEPTOR ALPHA; JANUS KINASE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; STAT PROTEIN; STEM CELL FACTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN;

ADAPTIVE IMMUNITY; ARTICLE; AUTOCRINE EFFECT; CELL DIFFERENTIATION; CELL GROWTH; CELL MIGRATION; CELL SURFACE; CRYSTAL STRUCTURE; EXTRACELLULAR SPACE; GENE OVEREXPRESSION; HUMAN; INNATE IMMUNITY; LYMPHOCYTE; MISSENSE MUTATION; MOLECULAR RECOGNITION; MUTAGENESIS; NONHUMAN; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION;

CRYSTALLOGRAPHY, X-RAY; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HUMANS; INFLAMMATION; INTERLEUKIN-3; INTERLEUKIN-5; LEUKEMIA, MYELOID; LYMPHOCYTES; MODELS, MOLECULAR; PROTEIN BINDING; RECEPTORS, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; RECEPTORS, INTERLEUKIN-3; RECEPTORS, INTERLEUKIN-5; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84867421584     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2012.01164.x     Document Type: Article

References (243)

1. Hercus TR, et al. The GM-CSF receptor family: mechanism of activation and implications for disease. Growth Factors 2012;30:63-75.
2. Lopez AF, et al. Molecular basis of cytokine receptor activation. IUBMB Life 2010;62:509-518.
3. Metcalf D. Hematopoietic cytokines. Blood 2008;111:485-491.
4. Nishinakamura R, Miyajima A, Mee PJ, Tybulewicz VL, Murray R. Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions. Blood 1996;88:2458-2464.
5. Hercus TR, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 2009;114:1289-1298.
6. Shibasaki T, et al. IL-3 can not replace GM-CSF in inducing human monocytes to differentiate into Langerhans cells. Int J Oncol 2007;30:49-55.
7. Goldstein JI, et al. Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease. Gastroenterology 2011;141:208-216.
8. Nylund CM, et al. Granulocyte-macrophage colony-stimulating factor autoantibodies and increased intestinal permeability in Crohn disease. J Pediatr Gastroenterol Nutr 2011;52:542-548.
9. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 2008;8:533-544.
10. 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;59:1087-1096.
11. Lantz CS, et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 1998;392:90-93.
12. Lopez AF, et al. Specific binding of human interleukin-3 and granulocyte-macrophage colony-stimulating factor to human basophils. J Allergy Clin Immunol 1990;85:99-102.
13. Kim S, Prout M, Ramshaw H, Lopez AF, LeGros G, Min B. Cutting edge: basophils are transiently recruited into the draining lymph nodes during helminth infection via IL-3, but infection-induced Th2 immunity can develop without basophil lymph node recruitment or IL-3. J Immunol 2010;184:1143-1147.
14. Lourenco FD, et al. Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus. Br J Dermatol 2008;158:979-986.
15. Budel LM, Touw IP, Delwel R, Clark SC, Lowenberg B. Interleukin-3 and granulocyte-monocyte colony-stimulating factor receptors on human acute myelocytic leukemia cells and relationship to the proliferative response. Blood 1989;74:565-571.
16. Jiang X, Lopez A, Holyoake T, Eaves A, Eaves C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia. Proc Natl Acad Sci USA 1999;96:12804-12809.
17. Delwel R, Dorssers L, Touw I, Wagemaker G, Lowenberg B. Human recombinant multilineage colony stimulating factor (interleukin-3): stimulator of acute myelocytic leukemia progenitor cells in vitro. Blood 1987;70:333-336.
18. Emanuel PD, Bates LJ, Castleberry RP, Gualtieri RJ, Zuckerman KS. Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 1991;77:925-929.
19. Riccioni R, et al. Interleukin (IL)-3/granulocyte macrophage-colony stimulating factor/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS-related tyrosine kinase 3 receptor. Br J Haematol 2009;144:376-387.
20. Testa U, et al. Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood 2002;100:2980-2988.
21. Zarogiannis S, Gourgoulianis KI, Kostikas K. Anti-interleukin-5 therapy and severe asthma. N Engl J Med 2009;360:2576; author reply 2577.
22. Asquith KL, Ramshaw HS, Hansbro PM, Beagley KW, Lopez AF, Foster PS. The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. J Immunol 2008;180:1199-1206.
23. Guthridge MA, et al. The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-kappaB and induction of bcl-2. Blood 2004;103:820-827.
24. Guthridge MA, et al. Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival. Mol Cell 2000;6:99-108.
25. 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;273:1192-1199.
26. Carpenter LR, Yancopoulos GD, Stahl N. General mechanisms of cytokine receptor signaling. Adv Protein Chem 1998;52:109-140.
27. Guthridge MA, et al. Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors. Stem Cells 1998;16:301-313.
28. Burgess AW, Camakaris J, Metcalf D. Purification and properties of colony-stimulating factor from mouse lung-conditioned medium. J Biol Chem 1977;252:1998-2003.
29. Codarri L, et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12:560-567.
30. El-Behi M, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011;12:568-575.
31. Fleetwood AJ, Cook AD, Hamilton JA. Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol 2005;25:405-428.
32. Sun Q, et al. Simultaneous antagonism of interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-3 stimulation of human eosinophils by targetting the common cytokine binding site of their receptors. Blood 1999;94:1943-1951.
33. Lampinen M, Carlson M, Hakansson LD, Venge P. Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy 2004;59:793-805.
34. Yamashita N, et al. Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cell Immunol 2002;219:92-97.
35. Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res 2001;3:293-298.
36. Niki Y, et al. Administration of cyclooxygenase-2 inhibitor reduces joint inflammation but exacerbates osteopenia in IL-1 alpha transgenic mice due to GM-CSF overproduction. J Immunol 2007;179:639-646.
37. Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol 1998;161:3639-3644.
38. Marusic S, et al. Local delivery of granulocyte-macrophage colony-stimulating factor by retrovirally transduced antigen-specific T cells leads to severe, chronic experimental autoimmune encephalomyelitis in mice. Neurosci Lett 2002;332:185-189.
39. Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 2007;178:39-48.
40. Kitching AR, Ru Huang X, Turner AL, Tipping PG, Dunn AR, Holdsworth SR. The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury. J Am Soc Nephrol 2002;13:350-358.
41. Timoshanko JR, Kitching AR, Semple TJ, Holdsworth SR, Tipping PG. Granulocyte macrophage colony-stimulating factor expression by both renal parenchymal and immune cells mediates murine crescentic glomerulonephritis. J Am Soc Nephrol 2005;16:2646-2656.
42. Lacey AA, Fleetwood AJ, et al. Defining GM-CSF and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol 2012;188:5752-5765.
43. Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell 2001;106:255-258.
44. Campbell IK, Bendele A, Smith DA, Hamilton JA. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis 1997;56:364-368.
45. Young DC, Wagner K, Griffin JD. Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia. J Clin Invest 1987;79:100-106.
46. Lajmanovich A, Berthier R, Schweitzer A, Leger J, Hollard D. Constitutive expression of GM-CSF mRNA by CML blast cells is correlated with endogenous megakaryocytic colony formation. Leukemia 1993;7:1211-1218.
47. Ramshaw HS, Bardy PG, Lee MA, Lopez AF. Chronic myelomonocytic leukemia requires granulocyte-macrophage colony-stimulating factor for growth in vitro and in vivo. Exp Hematol 2002;30:1124-1131.
48. Bernard F, et al. Transient hematologic and clinical effect of E21R in a child with end-stage juvenile myelomonocytic leukemia. Blood 2002;99:2615-2616.
49. Irish JM, et al. Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell 2004;118:217-228.
50. Kotecha N, et al. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell 2008;14:335-343.
51. Powell JA, et al. Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML. Blood 2009;114:4859-4870.
52. Kochetkova M, Iversen PO, Lopez AF, Shannon MF. Deoxyribonucleic acid triplex formation inhibits granulocyte macrophage colony-stimulating factor gene expression and suppresses growth in juvenile myelomonocytic leukemic cells. J Clin Invest 1997;99:3000-3008.
53. Birnbaum RA, et al. Nf1 and Gmcsf interact in myeloid leukemogenesis. Mol Cell 2000;5:189-195.
54. Kim A, et al. Beta common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood 2007;109:1687-1691.
55. Dranoff G, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 1994;264:713-716.
56. Stanley E, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA 1994;91:5592-5596.
57. Nishinakamura R, et al. Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal. Immunity 1995;2:211-222.
58. Robb L, et al. Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5. Proc Natl Acad Sci USA 1995;92:9565-9569.
59. Kitamura T, et al. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med 1999;190:875-880.
60. Inoue Y, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med 2008;177:752-762.
61. Suzuki T, et al. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med 2010;182:1292-1304.
62. Griese M, et al. Long-term follow-up and treatment of congenital alveolar proteinosis. BMC Pediatr 2011;11:72.
63. Tanaka T, et al. Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. J Med Genet 2011;48:205-209.
64. Suzuki T, et al. Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations. Eur Respir J 2011;37:201-204.
65. McCormack MP, Gonda TJ. Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the GM-CSF receptor beta subunit. Blood 2000;95:120-127.
66. Didichenko SA, Spiegl N, Brunner T, Dahinden CA. IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils. Blood 2008;112:3949-3958.
67. Weiss M, Yokoyama C, Shikama Y, Naugle C, Druker B, Sieff CA. Human granulocyte-macrophage colony-stimulating factor receptor signal transduction requires the proximal cytoplasmic domains of the alpha and beta subunits. Blood 1993;82:3298-3306.
68. Polotskaya A, Zhao Y, Lilly ML, Kraft AS. A critical role for the cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor alpha receptor in mediating cell growth. Cell Growth Differ 1993;4:523-531.
69. Dhar-Mascareno M, Chen J, Zhang RH, Carcamo JM, Golde DW. Granulocyte-macrophage colony-stimulating factor signals for increased glucose transport via phosphatidylinositol 3-kinase- and hydrogen peroxide-dependent mechanisms. J Biol Chem 2003;278:11107-11114.
70. Ebner K, Bandion A, Binder BR, de Martin R, Schmid JA. GMCSF activates NF-kappaB via direct interaction of the GMCSF receptor with IkappaB kinase beta. Blood 2003;102:192-199.
71. Tu J, Karasavvas N, Heaney ML, Vera JC, Golde DW. Molecular characterization of a granulocyte macrophage-colony-stimulating factor receptor alpha subunit-associated protein, GRAP. Blood 2000;96:794-799.
72. Perugini M, et al. Alternative modes of GM-CSF receptor activation revealed using activated mutants of the common beta-subunit. Blood 2010;115:3346-3353.
73. Liontos LM, Dissanayake D, Ohashi PS, Weiss A, Dragone LL, McGlade CJ. The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation. J Immunol 2011;186:1923-1933.
74. Wong GG, et al. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science 1985;228:810-815.
75. Rozwarski DA, Diederichs K, Hecht R, Boone T, Karplus PA. Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor. Proteins 1996;26:304-313.
76. Gearing DP, King JA, Gough NM, Nicola NA. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J 1989;8:3667-3676.
77. Hayashida K, Kitamura T, Gorman DM, Arai K, Yokota T, Miyajima A. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci USA 1990;87:9655-9659.
78. Hansen G, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 2008;134:496-507.
79. Carr PD, 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;104:291-300.
80. Carr PD, Conlan F, Ford S, Ollis DL, Young IG. An improved resolution structure of the human beta common receptor involved in IL-3, IL-5 and GM-CSF signalling which gives better definition of the high-affinity binding epitope. Acta Crystallogr Sect F Struct Biol Cryst Commun 2006;62:509-513.
81. Hercus TR, et al. Identification of residues in the first and fourth helices of human granulocyte-macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor. Blood 1994;83:3500-3508.
82. Rajotte D, et al. Crucial role of the residue R280 at the F′-G′ loop of the human granulocyte/macrophage colony-stimulating factor receptor alpha chain for ligand recognition. J Exp Med 1997;185:1939-1950.
83. Altmann SW, Kastelein RA. Rational design of a mouse granulocyte macrophage-colony-stimulating factor receptor antagonist. J Biol Chem 1995;270:2233-2240.
84. Mirza S, Walker A, Chen J, Murphy JM, Young IG. The Ig-like domain of human GM-CSF receptor alpha plays a critical role in cytokine binding and receptor activation. Biochem J 2010;426:307-317.
85. Lupardus PJ, Birnbaum ME, Garcia KC. Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2. Structure 2010;18:332-342.
86. Kusano S, et al. Structural basis of interleukin-5 dimer recognition by its alpha receptor. Protein Sci 2012;21:850-864.
87. Patino E, et al. Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like architecture for IL-5Ralpha. Structure 2011;19:1864-1875.
88. Barry SC, et al. Roles of the N and C terminal domains of the interleukin-3 receptor alpha chain in receptor function. Blood 1997;89:842-852.
89. Chen J, et al. A new isoform of interleukin-3 receptor {alpha} with novel differentiation activity and high affinity binding mode. J Biol Chem 2009;284:5763-5773.
90. LaPorte SL, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 2008;132:259-272.
91. Haman A, et al. Molecular determinants of the granulocyte-macrophage colony-stimulating factor receptor complex assembly. J Biol Chem 1999;274:34155-34163.
92. Suzuki T, et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med 2008;205:2703-2710.
93. Hercus TR, et al. Specific human granulocyte-macrophage colony-stimulating factor antagonists. Proc Natl Acad Sci USA 1994;91:5838-5842.
94. Woodcock JM, Bagley CJ, Zacharakis B, Lopez AF. A single tyrosine residue in the membrane-proximal domain of the granulocyte-macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 receptor common beta-chain is necessary and sufficient for high affinity binding and signaling by all three ligands. J Biol Chem 1996;271:25999-26006.
95. Shanafelt AB, Miyajima A, Kitamura T, Kastelein RA. The amino-terminal helix of GM-CSF and IL-5 governs high affinity binding to their receptors. EMBO J 1991;10:4105-4112.
96. Lopez AF, et al. Residue 21 of human granulocyte-macrophage colony-stimulating factor is critical for biological activity and for high but not low affinity binding. EMBO J 1992;11:909-916.
97. Meropol NJ, Altmann SW, Shanafelt AB, Kastelein RA, Johnson GD, Prystowsky MB. Requirement of hydrophilic amino-terminal residues for granulocyte-macrophage colony-stimulating factor bioactivity and receptor binding. J Biol Chem 1992;267:14266-14269.
98. McClure BJ, et al. Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex. Blood 2003;101:1308-1315.
99. Woodcock JM, et al. Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF. EMBO J 1994;13:5176-5185.
100. Shanafelt AB, Kastelein RA. High affinity ligand binding is not essential for granulocyte-macrophage colony-stimulating factor receptor activation. J Biol Chem 1992;267:25466-25472.
101. Barry SC, et al. Two contiguous residues in human interleukin-3, Asp21 and Glu22, selectively interact with the alpha- and beta-chains of its receptor and participate in function. J Biol Chem 1994;269:8488-8492.
102. Tavernier J, et al. Identification of receptor-binding domains on human interleukin 5 and design of an interleukin 5-derived receptor antagonist. Proc Natl Acad Sci USA 1995;92:5194-5198.
103. Rossjohn J, et al. Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist. Blood 2000;95:2491-2498.
104. 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;278:10572-10577.
105. Lock P, Metcalf D, Nicola NA. Histidine-367 of the human common beta chain of the receptor is critical for high-affinity binding of human granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci USA 1994;91:252-256.
106. Woodcock JM, McClure BJ, Stomski FC, Elliott MJ, Bagley CJ, Lopez AF. The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor exists as a preformed receptor complex that can be activated by GM-CSF, interleukin-3, or interleukin-5. Blood 1997;90:3005-3017.
107. Lupardus PJ, 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;19:45-55.
108. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993;234:779-815.
109. Metcalf D, Begley CG, Johnson GR, Nicola NA, Lopez AF, Williamson DJ. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood 1986;68:46-57.
110. Mach N, et al. Involvement of interleukin-3 in delayed-type hypersensitivity. Blood 1998;91:778-783.
111. Eder M, Geissler G, Ganser A. IL-3 in the clinic. Stem Cells 1997;15:327-333.
112. Vellenga E, Ostapovicz D, O'Rourke B, Griffin JD. Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures. Leukemia 1987;1:584-589.
113. Jin L, et al. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 2009;5:31-42.
114. Sun Q, et al. Monoclonal antibody 7G3 recognises the N-terminal domain of the human IL-3 receptor and functions as a specific IL-3 receptor antagonist. Blood 1996;87:83-92.
115. Brizzi MF, et al. Interleukin 3 stimulates proliferation and triggers endothelial-leukocyte adhesion molecule 1 gene activation of human endothelial cells. J Clin Invest 1993;91:2887-2892.
116. Korpelainen EI, et al. The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration. Proc Natl Acad Sci USA 1993;90:11137-11141.
117. Khew-Goodall Y, et al. Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3. Blood 1996;87:1432-1438.
118. Dentelli P, et al. Human IL-3 stimulates endothelial cell motility and promotes in vivo new vessel formation. J Immunol 1999;163:2151-2159.
119. Uberti B, Dentelli P, Rosso A, Defilippi P, Brizzi MF. Inhibition of beta1 integrin and IL-3Rbeta common subunit interaction hinders tumour angiogenesis. Oncogene 2010;29:6581-6590.
120. Haak-Frendscho M, Arai N, Arai K, Baeza ML, Finn A, Kaplan AP. Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release. J Clin Invest 1988;82:17-20.
121. Falcone FH, Haas H, Gibbs BF. The human basophil: a new appreciation of its role in immune responses. Blood 2000;96:4028-4038.
122. Lopez AF, et al. Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3. Proc Natl Acad Sci USA 1987;84:2761-2765.
123. Hida S, et al. Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils. Nat Immunol 2009;10:214-222.
124. Rothenberg ME, et al. Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3. J Clin Invest 1988;81:1986-1992.
125. Lopez AF, Eglinton JM, Gillis D, Park LS, Clark S, Vadas MA. Reciprocal inhibition of binding between interleukin 3 and granulocyte-macrophage colony-stimulating factor to human eosinophils. Proc Natl Acad Sci USA 1989;86:7022-7026.
126. Ichihara M, Hara T, Takagi M, Cho LC, Gorman DM, Miyajima A. Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor alpha subunit gene. EMBO J 1995;14:939-950.
127. Schroeder JT, Chichester KL, Bieneman AP. Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease. J Immunol 2009;182:2432-2438.
128. Till S, et al. Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colony-stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and non-atopic controls. Eur J Immunol 1995;25:2727-2731.
129. Shakoory B, Fitzgerald SM, Lee SA, Chi DS, Krishnaswamy G. The role of human mast cell-derived cytokines in eosinophil biology. J Interferon Cytokine Res 2004;24:271-281.
130. Yang YC, et al. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell 1986;47:3-10.
131. Feng Y, Klein BK, McWherter CA. Three-dimensional solution structure and backbone dynamics of a variant of human interleukin-3. J Mol Biol 1996;259:524-541.
132. Kitamura T, Sato N, Arai K, Miyajima A. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Cell 1991;66:1165-1174.
133. Gorman DM, et al. Cloning and expression of a gene encoding an interleukin 3 receptor-like protein: identification of another member of the cytokine receptor gene family. Proc Natl Acad Sci USA 1990;87:5459-5463.
134. Park LS, et al. Cloning of the low-affinity murine granulocyte-macrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex. Proc Natl Acad Sci USA 1992;89:4295-4299.
135. Devos R, et al. Molecular basis of a high affinity murine interleukin-5 receptor. EMBO J 1991;10:2133-2137.
136. Hara T, Miyajima A. Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3). EMBO J 1992;11:1875-1884.
137. Takaki S, et al. Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. EMBO J 1991;10:2833-2838.
138. Itoh N, et al. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Science 1990;247:324-327.
139. Lopez AF, et al. A human interleukin 3 analog with increased biological and binding activities. Proc Natl Acad Sci USA 1992;89:11842-11846.
140. Bagley CJ, Phillips J, Cambareri B, Vadas MA, Lopez AF. A discontinuous eight-amino acid epitope in human interleukin-3 binds the alpha-chain of its receptor. J Biol Chem 1996;271:31922-31928.
141. Klein BK, Feng Y, McWherter CA, Hood WF, Paik K, McKearn JP. The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling. J Biol Chem 1997;272:22630-22641.
142. Olins PO, et al. Saturation mutagenesis of human interleukin-3. J Biol Chem 1995;270:23754-23760.
143. Mirza S, et al. Two modes of beta-receptor recognition are mediated by distinct epitopes on mouse and human interleukin-3. J Biol Chem 2010;285:22370-22381.
144. Lokker NA, Zenke G, Strittmatter U, Fagg B, Movva NR. Structure-activity relationship study of human interleukin-3: role of the C-terminal region for biological activity. EMBO J 1991;10:2125-2131.
145. Murphy JM, et al. Interleukin-3 binding to the murine betaIL-3 and human betac receptors involves functional epitopes formed by domains 1 and 4 of different protein chains. J Biol Chem 2004;279:26500-26508.
146. Yao S, Young IG, Norton RS, Murphy JM. Murine interleukin-3: structure, dynamics, and conformational heterogeneity in solution. Biochemistry 2011;50:2464-2477.
147. Milburn MV, et al. A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5. Nature 1993;363:172-176.
148. Dey R, Ji K, Liu Z, Chen L. A cytokine-cytokine interaction in the assembly of higher-order structure and activation of the interleukine-3: receptor complex. PLoS One 2009;4:e5188.
149. Lokker NA, Movva NR, Strittmatter U, Fagg B, Zenke G. Structure-activity relationship study of human interleukin-3 Identification of residues required for biological activity by site-directed mutagenesis. J Biol Chem 1991;266:10624-10631.
150. Lokker NA, et al. Mapping the epitopes of neutralizing anti-human IL-3 monoclonal antibodies Implications for structure-activity relationship. J Immunol 1991;146:893-898.
151. Sanderson CJ, Warren DJ, Strath M. Identification of a lymphokine that stimulates eosinophil differentiation in vitro Its relationship to interleukin 3, and functional properties of eosinophils produced in cultures. J Exp Med 1985;162:60-74.
152. Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ. Murine eosinophil differentiation factor An eosinophil-specific colony-stimulating factor with activity for human cells. J Exp Med 1986;163:1085-1099.
153. 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;167:219-224.
154. Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood 1992;79:3101-3109.
155. Yamaguchi Y, Suda T, Ohta S, Tominaga K, Miura Y, Kasahara T. Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils. Blood 1991;78:2542-2547.
156. Fujisawa T, Abu-Ghazaleh R, Kita H, Sanderson CJ, Gleich GJ. Regulatory effect of cytokines on eosinophil degranulation. J Immunol 1990;144:642-646.
157. Denburg JA, Silver JE, Abrams JS. Interleukin-5 is a human basophilopoietin: induction of histamine content and basophilic differentiation of HL-60 cells and of peripheral blood basophil-eosinophil progenitors. Blood 1991;77:1462-1468.
158. Bischoff SC, Brunner T, De Weck AL, Dahinden CA. Interleukin 5 modifies histamine release and leukotriene generation by human basophils in response to diverse agonists. J Exp Med 1990;172:1577-1582.
159. Hirai K, et al. Enhancement of human basophil histamine release by interleukin 5. J Exp Med 1990;172:1525-1528.
160. Ying S, et al. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1997;158:3539-3544.
161. Broide DH, Paine MM, Firestein GS. Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics. J Clin Invest 1992;90:1414-1424.
162. Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 1997;156:704-708.
163. Corrigan CJ, et al. CD4 T-lymphocyte activation in asthma is accompanied by increased serum concentrations of interleukin-5. Effect of glucocorticoid therapy. Am Rev Respir Dis 1993;147:540-547.
164. Lampinen M, Rak S, Venge P. The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 1999;29:314-322.
165. Garrett JK, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 2004;113:115-119.
166. Rothenberg ME, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358:1215-1228.
167. Nair P, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-993.
168. Haldar P, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-984.
169. Leckie MJ, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-2148.
170. Flood-Page P, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007;176:1062-1071.
171. Wenzel SE, et al. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 1999;160:1001-1008.
172. Azuma C, et al. Cloning of cDNA for human T-cell replacing factor (interleukin-5) and comparison with the murine homologue. Nucleic Acids Res 1986;14:9149-9158.
173. Wells TN, et al. The three-dimensional structure of human interleukin-5 at 2.4-angstroms resolution: implication for the structures of other cytokines. Ann NY Acad Sci 1994;725:118-127.
174. Tavernier J, et al. 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 1991;66:1175-1184.
175. Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K. Molecular cloning and expression of the human interleukin 5 receptor. J Exp Med 1992;175:341-351.
176. Ishino T, Harrington AE, Zaks-Zilberman M, Scibek JJ, Chaiken I. Slow-dissociation effect of common signaling subunit beta c on IL5 and GM-CSF receptor assembly. Cytokine 2008;42:179-190.
177. Scibek JJ, Evergren E, Zahn S, Canziani GA, Van Ryk D, Chaiken IM. Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c) interaction with IL5:IL5R(alpha) complexes. Anal Biochem 2002;307:258-265.
178. Zaks-Zilberman M, Harrington AE, Ishino T, Chaiken IM. Interleukin-5 receptor subunit oligomerization and rearrangement revealed by fluorescence resonance energy transfer imaging. J Biol Chem 2008;283:13398-13406.
179. Cornelis S, et al. Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor. EMBO J 1995;14:3395-3402.
180. Ishino T, Pasut G, Scibek J, Chaiken I. Kinetic interaction analysis of human interleukin 5 receptor alpha mutants reveals a unique binding topology and charge distribution for cytokine recognition. J Biol Chem 2004;279:9547-9556.
181. McKenzie AN, Barry SC, Strath M, Sanderson CJ. Structure-function analysis of interleukin-5 utilizing mouse/human chimeric molecules. EMBO J 1991;10:1193-1199.
182. Johanson K, et al. Binding interactions of human interleukin 5 with its receptor alpha subunit Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J Biol Chem 1995;270:9459-9471.
183. Morton TA, et al. Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. J Mol Recognit 1994;7:47-55.
184. Cornelis S, et al. Characterization of critical residues in the cytoplasmic domain of the human interleukin-5 receptor alpha chain required for growth signal transduction. Eur J Immunol 1995;25:1857-1864.
185. Morton T, Li J, Cook R, Chaiken I. Mutagenesis in the C-terminal region of human interleukin 5 reveals a central patch for receptor alpha chain recognition. Proc Natl Acad Sci USA 1995;92:10879-10883.
186. Wu SJ, et al. Randomization of the receptor alpha chain recruitment epitope reveals a functional interleukin-5 with charge depletion in the CD loop. J Biol Chem 1999;274:20479-20488.
187. Bhattacharya M, et al. Recruitment pharmacophore for interleukin 5 receptor alpha antagonism. Biopolymers 2007;88:83-93.
188. England BP, et al. A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains. Proc Natl Acad Sci USA 2000;97:6862-6867.
189. Ishino T, et al. Asymmetric usage of antagonist charged residues drives interleukin-5 receptor recruitment but is insufficient for receptor activation. Biochemistry 2006;45:1106-1115.
190. Ishino T, Urbina C, Bhattacharya M, Panarello D, Chaiken I. Receptor epitope usage by an interleukin-5 mimetic peptide. J Biol Chem 2005;280:22951-22961.
191. Li J, Cook R, Chaiken I. Mutants of single chain interleukin 5 show asymmetric recruitment of receptor alpha and betac subunits. J Biol Chem 1996;271:31729-31734.
192. Li J, Cook R, Dede K, Chaiken I. Single chain human interleukin 5 and its asymmetric mutagenesis for mapping receptor binding sites. J Biol Chem 1996;271:17-20.
193. Broughton SE, Hercus TR, Lopez AF, Parker MW. Cytokine receptor activation at the cell surface. Curr Opin Struct Biol 2012;22:350-359.
194. Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam S-Y, Galli SJ. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 2005;167:835-848.
195. Chen CC, Grimbaldeston MA, Tsai M, Weissman IL, Galli SJ. Identification of mast cell progenitors in adult mice. Proc Natl Acad Sci USA 2005;102:11408-11413.
196. Czechowicz A, Weissman IL. Purified hematopoietic stem cell transplantation: the next generation of blood and immune replacement. Immunol Allergy Clin North Am 2010;30:159-171.
197. Seita J, Weissman IL. Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med 2010;2:640-653.
198. Ye ZJ, Gulcicek E, Stone K, Lam T, Schulz V, Weissman SM. Complex interactions in EML cell stimulation by stem cell factor and IL-3. Proc Natl Acad Sci USA 2011;108:4882-4887.
199. Chen J, Carcamo JM, Golde DW. The alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling. J Biol Chem 2006;281:22421-22426.
200. Scott CL, Robb L, Papaevangeliou B, Mansfield R, Nicola NA, Begley CG. Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor. Blood 2000;96:1588-1590.
201. Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 2009;10:713-720.
202. Perrigoue JG, et al. MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 2009;10:697-705.
203. Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as "tunable" effector and immunoregulatory cells: recent advances. Annu Rev Immunol 2005;23:749-786.
204. Kraft S, Kinet JP. New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 2007;7:365-378.
205. Andreu P, et al. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 2010;17:121-134.
206. Stohlman F Jr., Ebbe S, Morse B, Howard D, Donovan J. Regulation of erythropoiesis XX. Kinetics of red cell production. Ann N Y Acad Sci 1968;149:156-172.
207. Lombardero M, Kovacs K, Scheithauer BW. Erythropoietin: a hormone with multiple functions. Pathobiology 2011;78:41-53.
208. Juul SE. Nonerythropoietic roles of erythropoietin in the fetus and neonate. Clin Perinatol 2000;27:527-541.
209. Buemi M, et al. Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps. Acta Derm Venereol 2002;82:411-417.
210. Faquin WC, Schneider TJ, Goldberg MA. Effect of inflammatory cytokines on hypoxia-induced erythropoietin production. Blood 1992;79:1987-1994.
211. Bar-Or D, Thomas G. Beneficial effects of carbamylated erythropoeitin on trauma-induced brain edema: proposed molecular mechanisms of action. Crit Care Med 2011;39:2191.
212. Brines M, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci USA 2008;105:10925-10930.
213. Bonder CS, et al. Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation. Blood 2009;113:2108-2117.
214. Ribatti D, et al. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999;93:2627-2636.
215. Yasuda Y, Masuda S, Chikuma M, Inoue K, Nagao M, Sasaki R. Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J Biol Chem 1998;273:25381-25387.
216. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 2002;64:326-333.
217. Miskowiak K, O'Sullivan U, Harmer CJ. Erythropoietin enhances hippocampal response during memory retrieval in humans. J Neurosci 2007;27:2788-2792.
218. Ehrenreich H, et al. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry 2007;12:206-220.
219. Boissel JP, Lee WR, Presnell SR, Cohen FE, Bunn HF. Erythropoietin structure-function relationships: mutant proteins that test a model of tertiary structure. J Biol Chem 1993;268:15983-15993.
220. Cheetham JC, et al. NMR structure of human erythropoietin and a comparison with its receptor bound conformation. Nat Struct Biol 1998;5:861-866.
221. Elliott S, Lorenzini T, Chang D, Barzilay J, Delorme E. Mapping of the active site of recombinant human erythropoietin. Blood 1997;89:493-502.
222. Wen D, Boissel JP, Showers M, Ruch BC, Bunn HF. Erythropoietin structure-function relationships. Identification of functionally important domains. J Biol Chem 1994;269:22839-22846.
223. Leist M, et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004;305:239-242.
224. Hanazono Y, Sasaki K, Nitta H, Yazaki Y, Hirai H. Erythropoietin induces tyrosine phosphorylation of the beta chain of the GM-CSF receptor. Biochem Biophys Res Commun 1995;208:1060-1066.
225. Miura O, D'Andrea A, Kabat D, Ihle JN. Induction of tyrosine phosphorylation by the erythropoietin receptor correlates with mitogenesis. Mol Cell Biol 1991;11:4895-4902.
226. Jubinsky PT, Krijanovski OI, Nathan DG, Tavernier J, Sieff CA. The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor. Blood 1997;90:1867-1873.
227. Blake TJ, Jenkins BJ, D'Andrea RJ, Gonda TJ. Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the beta-subunit of the GM-CSF receptor. J Leukoc Biol 2002;72:1246-1255.
228. Sieff CA, Ekern SC, Nathan DG, Anderson JW. Combinations of recombinant colony-stimulating factors are required for optimal hematopoietic differentiation in serum-deprived culture. Blood 1989;73:688-693.
229. Goodman JW, Hall EA, Miller KL, Shinpock SG. Interleukin 3 promotes erythroid burst formation in "serum-free" cultures without detectable erythropoietin. Proc Natl Acad Sci USA 1985;82:3291-3295.
230. Brines M, et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci USA 2004;101:14907-14912.
231. Heeschen C, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003;102:1340-1346.
232. Bahlmann FH, et al. Erythropoietin regulates endothelial progenitor cells. Blood 2004;103:921-926.
233. Takahashi T, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434-438.
234. Sautina L, et al. Induction of nitric oxide by erythropoietin is mediated by the {beta} common receptor and requires interaction with VEGF receptor 2. Blood 2010;115:896-905.
235. Su KH, et al. beta Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. J Cell Physiol 2011;226:3330-3339.
236. Murohara T, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 1998;101:2567-2578.
237. Urbich C, Dimmeler S. Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. Kidney Int 2005;67:1672-1676.
238. Saulle E, et al. Colocalization of the VEGF-R2 and the common IL-3/GM-CSF receptor beta chain to lipid rafts leads to enhanced p38 activation. Br J Haematol 2009;145:399-411.
239. Dentelli P, et al. The interaction between KDR and interleukin-3 receptor (IL-3R) beta common modulates tumor neovascularization. Oncogene 2005;24:6394-6405.
240. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931-10934.
241. Lyden D, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001;7:1194-1201.
242. Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964-967.
243. Defilippi P, et al β1 integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation. J Cell Biol 2005;168:1099-1108.