IL-4 receptor complexes containing or lacking the gamma C chain are inhibited by an overlapping set of antagonistic IL-4 mutant proteins.
IL-4 signals on lymphocytes and other cells through a heterodimeric complex of two cytokine receptor proteins, IL-4R alpha and gamma C. IL-4 variants with mutations in the positions Tyr124, and (less efficiently) Arg121 and Ser125 are deficient in interaction with gamma zero and can be applied as IL-4 antagonists. Some cells respond to IL-4 without using gamma zero presumably by recruiting an alternative subunit into the receptor complex. We have investigated the effects of IL-4 mutant proteins on cells bearing this second type of IL-4 receptor complex. Mutations in the amino acid residues Arg 121 and Tyr124, but not Ser125, completely prevented cellular responses mediated by type 2 IL-4 receptors. Both receptor types are therefore affected by mutations in an overlapping but not identical site of the IL-4 molecule.
Schnarr
B
B
Theodor-Boveri-Institut für Biowissenschaften (Biozentrum), Wuerzburg, Germany.
Ezernieks
J
J
Sebald
W
W
Duschl
A
A
D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D018123:Receptors, Interleukin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000494:pharmacology; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006131:Growth Inhibitors; D008024:Ligands; D010446:Peptide Fragments; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4