Open AccessDifferent Human Interleukin‐4 Mutants Preferentially Activate Human or Murine Common Receptor γ Chain
Author(s) -
Lischke Antje,
Kammer Winfried,
Friedrich Karlheinz
Publication year - 1995
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1995.100_c.x
Subject(s) - common gamma chain , alpha chain , receptor , interleukin 10 receptor, alpha subunit , biology , mutant , microbiology and biotechnology , interleukin 5 receptor alpha subunit , interleukin 4 receptor , transfection , signal transduction , interleukin 4 , interleukin 21 receptor , g alpha subunit , cell culture , cytokine , protein subunit , biochemistry , immunology , gene , genetics
Interleukin‐4 (IL‐4) shows species‐specific activity due to species‐restricted interaction with the IL‐4 receptor α (IL‐4Rα) chain. The second subunit of a functional IL‐4 receptor, the common γ chain (γ c ), is more promiscuous, since human IL‐4 is able to activate IL‐4 receptor complexes containing either human or murine common γ receptor chain (γ c ). We have stably transfected factor‐dependent mouse cells of myeloid and lymphoid origin with combinations of human IL‐4Rα and γ c . derivatives. In these cell lines, both human and murine γ c receptors as well as IL‐4Rα chains from both species are simultaneously expressed. Both versions of γ c readily form ternary complexes with either human IL‐4 and human IL‐4Rα or murine IL‐4 and murine IL‐4Rα. Due to distinct ligand‐binding properties of human and murine γ c , the two receptor complexes can be activated preferentially by different mutant variants of human IL‐4. The contribution of murine common γ chain to human IL‐4‐induced signal transduction is suppressed by an inhibitory antibody directed to the extracellular domain of the mouse γ c . We present evidence that the two IL‐4R complexes functionally interfere with each other and compete for response‐limiting signalling components.