An antagonistic mutant of interleukin-4 fails to recruit gamma c into the receptor complex. Characterization by specific crosslinking.
The receptor for interleukin-4 (IL-4) appears to be a heterodimer of the IL-4-binding protein IL-4R alpha and the gamma c chain. Mutations of IL-4 have previously identified a region of IL-4 essential for signaling, which was suggested to bind gamma c. Here it is shown by crosslinking of radiolabeled ligand and precipitation with specific antibodies that mutations in the IL-4 signaling site prevent association of gamma c, but not binding to IL-4R alpha. This demonstrates that an intact signaling site of IL-4 is required to recruit gamma c into the receptor complex, while specific mutants are antagonists because they fail to achieve this.
Duschl
A
A
Theodor-Boveri-Institute für Biowissenschaften, Würzburg, Germany.
D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009154:Mutation; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007074:Immunoglobulin G; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4