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J. Biol. Chem., Vol. 277, Issue 48, 46073-46078, November 29, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/48/46073    most recent M209560200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andrews, A.-L. Articles by Davies, D. E. Search for Related Content PubMed PubMed Citation Articles by Andrews, A.-L. Articles by Davies, D. E. Social Bookmarking                      What's this?

Kinetic Analysis of the Interleukin-13 Receptor Complex^*

Allison-Lynn Andrews, John W. Holloway, Sarah M. Puddicombe, Stephen T. Holgate, and Donna E. Davies^§

From the Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, 97 Tremona Rd., Southampton General Hospital, Southampton SO16 6YD, United Kingdom

Interleukin (IL)-13 is a key cytokine associated with the asthmatic phenotype. It signals via its cognate receptor, a complex of IL-13 receptor 1 chain (IL-13R1) with IL-4R; however, a second protein, IL-13R2, also binds IL-13. To determine the binding contributions of the individual components of the IL-13 receptor to IL-13, we have employed surface plasmon resonance and equilibrium binding assays to investigate the ligand binding characteristics of shIL-13R1, shIL-13R2, and IL-4R. shIL-13R1 bound IL-13 with moderate affinity (K_D = 37.8 ± 1.8 nM, n = 10), whereas no binding was observed for hIL-4R. In contrast, shIL-13R2 produced a high affinity interaction with IL-13 (K_D = 2.49 ± 0.94 nM n = 10). IL-13R2 exhibited the binding characteristics of a negative regulator with a fast association rate and an exceptional slow dissociation rate. Although IL-13 interacted weakly with IL-4R on its own (K_D > 50 µM), the presence of hIL-4R significantly increased the affinity of shIL-13R1 for IL-13 but had no effect on the binding affinity of IL-13R2. Detailed kinetic analyses of the binding properties of the heteromeric complexes suggested a sequential mechanism for the binding of IL-13 to its signaling receptor, in which IL-13 first binds to IL-13R1 and this then recruits IL-4R to stabilize a high affinity interaction.

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