Binding of IL‐4 to the IL‐13Rα₁/IL‐4Rα receptor complex leads to STAT3 phosphorylation but not to its nuclear translocation

Abstract

Interleukin-4 (IL-4) is a pleiotropic cytokine, which acts on both hematopoietic and non-hematopoietic cells, through different types of receptor complexes. In this study, we report that in human B cells, IL-4 caused rapid phosphorylation of Janus kinase (JAK) 1 and JAK3 tyrosine kinases. In keratinocytes, the hematopoietic-specific receptor common Q Q c chain is not expressed and the IL-13 receptor K K 1 (IL-13RK K 1 ) participates in IL-4 signal transduction. In keratinocytes, IL-4 induced JAK1 and JAK2 phosphorylation but, unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling. In both cell types, IL-4 induced phosphorylation and DNA binding activation of the signal transducer and activator of transcription (STAT) 6 protein. Furthermore, IL-4 stimulation of keratinocytes also induced tyrosine phosphorylation of STAT3 which was found to bind to the phosphorylated IL-13RK K 1 . STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.z 1999 Federation of European Biochemical Societies.

IL-4 regulation of IL-6 production involves Rac/Cdc42- and p38 MAPK-dependent pathways in keratinocytes

“…The results presented here are consistent with our previous ®ndings which have indicated that in keratinocytes, in contrast to hematopoietic cell lines, IL-4 also induced ERK activation (Wery et al, 1996). In A431 cells, we and others have demonstrated that the nature of the IL-4R is dierent from hematopoietic cell lines (Murata et al, 1997;Wery-Zennaro et al, 1999). The characterization of IL-4R, reported in a larger number of cell lines, indicated that only hematopoietic cells signi®cantly expressed g c .…”

Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4

“…precipitation assay was carried out as described previously (34). In brief, the following 59 biotin-labeled single-stranded oligonucleotides were hybridized: 59-ACT GCG AAC ATT TCG CTT TCATTT TGG-39 and 59-CCA AAATGA AAG CGA AAT GTT CGC AGT-39 (MWG Biotech, Ebersberg, Germany) according to the human IFN sequence response element (ISRE) consensus sequence from the IL-12p35 promoter.…”

STAT6 and Ets-1 Form a Stable Complex That Modulates Socs-1 Expression by Interleukin-4 in Keratinocytes

“…The Jak-STAT pathway has been shown to be activated by IL-4. Activation of JAK1 and JAK2 or 3, depending on the cell lines, is pivotal for the activation of downstream signaling events including the recruitment and rapid tyrosine phosphorylation of STAT6 (1)(2)(3)(4). STAT6 can dimerize and translocate into the nucleus where it regulates IL-4 target genes.…”