Interleukin-11 signals through the formation of a hexameric receptor complex

Citation
Va. Barton et al., Interleukin-11 signals through the formation of a hexameric receptor complex, J BIOL CHEM, 275(46), 2000, pp. 36197-36203
Citations number
50
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
46
Year of publication
2000
Pages
36197 - 36203
Database
ISI
SICI code
0021-9258(20001117)275:46<36197:ISTTFO>2.0.ZU;2-F
Abstract
Interleukin-11 (IL-11) is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of whi ch contain at least one molecule of the transmembrane signaling receptor gp 130. IL-11 has been shown to induce gp130-dependent signaling through the f ormation of a high affinity complex with the IL-11 receptor (IL-11R) and gp 130. Site-directed mutagenesis studies have identified three distinct recep tor binding sites of IL-11, which enable it to form this high affinity rece ptor complex. Here we present data from immunoprecipitation experiments, us ing differentially tagged forms of ligand and soluble receptor components, which show that multiple copies of IL-11, IL-11R, and gp130 are present in the receptor complex. Furthermore, it is demonstrated that sites II and III of IL-11 are independent gp130 binding epitopes and that both are essentia l for gp130 dimerization. We also show that a stable high affinity complex of IL-11, IL-11R, and gp130 can be resolved by nondenaturing polyacrylamide gel electrophoresis, and its composition verified by second dimension dena turing polyacrylamide gel electrophoresis. Results indicate that the three receptor binding sites of IL-11 and the Ig-like domain of gp130 are all ess ential for this stable receptor complex to be formed. We therefore propose that IL-11 forms a hexameric receptor complex composed of two molecules eac h of IL-11, IL-11R, and gp130.