Homodimerization of interleukin-4 receptor alpha chain can induce intracellular signaling.

The possible role of homodimerization events in intracellular signal transduction triggered by the bipartite human interleukin-4 receptor was addressed. We generated cell lines functionally expressing derivatives of the two receptor subunits alpha and gamma, which allow for a specific and background-free experimental induction of intracellular homo- and heterodimers. A heterodimer of alpha and gamma released an intracellular signal, whereas a gamma-gamma homodimer did not. Unexpectedly, we found the intracellular domain of interleukin-4 receptor alpha chain to evoke cell proliferation and activation of tyrosine kinase Jak1 as well as of transcription factor Stat6 upon homodimerization. Both recruitment of the common gamma chain and activation of kinase Jak3 were shown to be dispensible for these processes.