Cytoplasmic domains of the interleukin-2 receptor β and γ chains mediate the signal for T-cell proliferation

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Abstract
THE interleukin-2 receptor (IL-2R) consists of three distinct chains (α, β, γ) which bind IL-2 and generate a proliferative signal in T cells1. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2Rβ or IL-2Rγ and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF) 2. We report here that binding of SCF to the β-chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the β- and γ-chain chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor β and γ chains constructed with the heterodimeric extracellular regions of the granulocyte–macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2Rβ and -γ appears necessary and sufficient for signalling in T cells.