Different human interleukin-4 mutants preferentially activate human or murine common receptor gamma chain.
Interleukin-4 (IL-4) shows species-specific activity due to species-restricted interaction with the IL-4 receptor alpha (IL-4R alpha) chain. The second subunit of a functional IL-4 receptor, the common gamma chain (gamma c), is more promiscuous, since human IL-4 is able to activate IL-4 receptor complexes containing either human or murine common gamma receptor chain (gamma c). We have stably transfected factor-dependent mouse cells of myeloid and lymphoid origin with combinations of human IL-4R alpha and gamma c derivatives. In these cell lines, both human and murine gamma c receptors as well as IL-4R alpha chains from both species are simultaneously expressed. Both versions of gamma c readily form ternary complexes with either human IL-4 and human IL-4R alpha or murine IL-4 and murine IL-4R alpha. Due to distinct ligand-binding properties of human and murine gamma c, the two receptor complexes can be activated preferentially by different mutant variants of human IL-4. The contribution of murine common gamma chain to human IL-4-induced signal transduction is suppressed by an inhibitory antibody directed to the extracellular domain of the mouse gamma c. We present evidence that the two IL-4R complexes functionally interfere with each other and compete for response-limiting signalling components.
Theodor-Boveri-Institut für Biowissenschaften, Würzburg, Germany.
A
A
Lischke
W
W
Kammer
K
K
Friedrich
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D015398:Signal Transduction
D015703:Antigens, CD; D017931:DNA Primers; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4