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

FEBS Letters

Wery-Zennaro, Sandrine¹  David, Muriel¹  Bertoglio, Jacques¹  Pierre, Josiane¹  Letourneur, Martine¹ 

[1] INSERM U461, Faculté de Pharmacie, 5, rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France

关键词: Nuclear localization;    Signal transducer and activator of transcription;    Janus kinase;    Signal transduction;    Cytokine receptor;    Keratinocyte;    EGF;    epidermal growth factor;    EMSA;    electrophoretic mobility shift assay;    GAS;    γ-interferon-activated sequence;    GSH;    glutathione;    GST;    glutathione S-transferase;    IL;    interleukin;    IL-4R;    IL-4 receptor;    IL-13R;    IL-13 receptor;    JAK;    Janus kinase;    PAGE;    polyacrylamide gel electrophoresis;    RT-PCR;    reverse transcriptase polynucleotide chain reaction;    SH2;    Src homology 2;    SIE;    sis-inducible element;    STAT;    signal transducer and activator of transcription;   

DOI  :  10.1016/S0014-5793(99)01680-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 γ_c chain is not expressed and the IL-13 receptor α₁ (IL-13Rα₁) 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-13Rα₁. STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.

【 授权许可】

Unknown