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2: Molecular Cloning, Characterization, and Comparison with Murine IL-13 Receptor 11
*
Genetics Institute, Immunology Department, Cambridge, MA 02140; and
Brigham and Women’s Hospital, Division of Genetics, Boston, MA 02115
Two components of a receptor complex for IL-13, the IL-4R and a low
affinity IL-13-binding chain, IL-13R
1, have been cloned in mice and
humans. An additional high affinity binding chain for IL-13,
IL-13R2, has been described in humans. We isolated a cDNA from the
thymus that encodes the murine orthologue of the human IL-13R2. The
predicted protein sequence of murine IL-13R2 (mIL-13R2)
has 59% overall identity to human IL-13R2 and is closely related to
the murine low affinity IL-13-binding subunit, IL-13R1. The genes
for both mIL-13-binding chains map to the X chromosome. A specific
interaction between mIL-13R2.Fc protein and IL-13 was demonstrated
by surface plasmon resonance using a BIACORE instrument. Ba/F3
cells that were transfected with mIL-13R2 expressed 5000 molecules
per cell and bound IL-13 with a single Kd of
0.5 to 1.2 nM. However, these cells did not proliferate in response to
IL-13, and the IL-4 dose response was unaffected by high concentrations
of IL-13. In contrast, the expression of mIL-13R1 by Ba/F3 cells
resulted in a sensitive proliferative response to IL-13. Consistent
with its lower affinity for IL-13, IL-13R1.Fc was 100-fold less
effective than IL-13R2.Fc in neutralizing IL-13 in vitro. These
results show that mIL-13R2 and mIL-13R1 are not functionally
equivalent and predict distinct roles for each polypeptide in IL-13R
complex formation and in the modulation of IL-13 signal
transduction.
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W. R. Henderson Jr., E. Y. Chi, and C. R. Maliszewski Soluble IL-4 Receptor Inhibits Airway Inflammation Following Allergen Challenge in a Mouse Model of Asthma J. Immunol., January 15, 2000; 164(2): 1086 - 1095. [Abstract] [Full Text] [PDF]
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 P. L. Jensen The Interleukin 13 Receptor Complex Stem Cells, January 1, 2000; 18(1): 61 - 62. [Full Text]
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D. Ford, C. Sheehan, C. Girasole, R. Priester, N. Kouttab, J. Tigges, T. C. King, A. Luciani, J. W. Morgan, and A. L. Maizel The Human B Cell Response to IL-13 Is Dependent on Cellular Phenotype as Well as Mode of Activation J. Immunol., September 15, 1999; 163(6): 3185 - 3193. [Abstract] [Full Text] [PDF]
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J. Poudrier, P. Graber, S. Herren, D. Gretener, G. Elson, C. Berney, J.-F. Gauchat, and M. H. Kosco-Vilbois A Soluble Form of IL-13 Receptor {alpha}1 Promotes IgG2a and IgG2b Production by Murine Germinal Center B Cells J. Immunol., August 1, 1999; 163(3): 1153 - 1161. [Abstract] [Full Text] [PDF]
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P. L. Orchansky, R. Kwan, F. Lee, and J. W. Schrader Characterization of the Cytoplasmic Domain of Interleukin-13 Receptor-alpha J. Biol. Chem., July 23, 1999; 274(30): 20818 - 20825. [Abstract] [Full Text] [PDF]
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N. Noben-Trauth, W. E. Paul, and D. L. Sacks IL-4- and IL-4 Receptor-Deficient BALB/c Mice Reveal Differences in Susceptibility to Leishmania major Parasite Substrains J. Immunol., May 15, 1999; 162(10): 6132 - 6140. [Abstract] [Full Text] [PDF]
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M. G. Chiaramonte, L. R. Schopf, T. Y. Neben, A. W. Cheever, D. D. Donaldson, and T. A. Wynn IL-13 Is a Key Regulatory Cytokine for Th2 Cell-Mediated Pulmonary Granuloma Formation and IgE Responses Induced by Schistosoma mansoni Eggs J. Immunol., January 15, 1999; 162(2): 920 - 930. [Abstract] [Full Text] [PDF]
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 M. Wills-Karp, J. Luyimbazi, X. Xu, B. Schofield, T. Y. Neben, C. L. Karp, and D. D. Donaldson Interleukin-13: Central Mediator of Allergic Asthma Science, December 18, 1998; 282(5397): 2258 - 2261. [Abstract] [Full Text]
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G. Grünig, M. Warnock, A. E. Wakil, R. Venkayya, F. Brombacher, D. M. Rennick, D. Sheppard, M. Mohrs, D. D. Donaldson, R. M. Locksley, et al. Requirement for IL-13 Independently of IL-4 in Experimental Asthma Science, December 18, 1998; 282(5397): 2261 - 2263. [Abstract] [Full Text]
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