Wery-Zennaro S, Letourneur M, David M, Bertoglio J, Pierre J
INSERM U461, Faculté de Pharmacie, 5, rue J.B. Clément, 92296, Châtenay-Malabry, France.
FEBS Lett. 1999 Dec 24;464(1-2):91-6. doi: 10.1016/s0014-5793(99)01680-4.
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 gamma(c) chain is not expressed and the IL-13 receptor alpha(1) (IL-13Ralpha(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-13Ralpha(1). STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.
白细胞介素-4(IL-4)是一种多效性细胞因子,它通过不同类型的受体复合物作用于造血细胞和非造血细胞。在本研究中,我们报告在人B细胞中,IL-4可导致Janus激酶(JAK)1和JAK3酪氨酸激酶快速磷酸化。在角质形成细胞中,不表达造血特异性受体共同γ(c)链,而IL-13受体α(1)(IL-13Rα(1))参与IL-4信号转导。在角质形成细胞中,IL-4可诱导JAK1和JAK2磷酸化,但与免疫细胞不同的是,IL-4信号传导不涉及JAK3激活。在这两种细胞类型中,IL-4均可诱导信号转导和转录激活因子(STAT)6蛋白的磷酸化及DNA结合激活。此外,IL-4刺激角质形成细胞还可诱导STAT3酪氨酸磷酸化,发现其与磷酸化的IL-13Rα(1)结合。然而,STAT3并未明显转位至细胞核,也未以高亲和力与靶DNA序列结合。