JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis

✍ Scribed by Wei-Hwa Lee; Fu-Hwa Liu; John Yi-Chung Lin; Shih-Yun Huang; Heng Lin; Wei-Ju Liao; Huei-Mei Huang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 243 KB
• Volume: 106
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22069

✦ Synopsis

Abstract

Interleukin‐5 (IL‐5) induction of c‐Myc expression is associated with IL‐5 inhibition of apoptosis in hematopoietic cells. In this study, TFα1 and TFα8 cells with stable overexpression of IL‐5 receptor α (IL‐5Rα) subunit in TF‐1 cells, a human hematopoietic progenitor cell line which expressed low levels of IL‐5Rα, were used to explored how IL‐5 up‐regulate c‐Myc and the role of c‐Myc in IL‐5 signaling. First, we demonstrate that IL‐5 induced c‐Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and JAK2) and signal transducer and activator of transcription‐5b (STAT5b). JAK inhibitor AG490 and c‐Myc inhibitor 10058‐F4, both, reduced IL‐5‐mediated cell proliferation in a dose‐ and time‐dependent manner. Both, AG490 and 10058‐F4, also reduced IL‐5‐mediated anti‐apoptotic activity. Furthermore, AG490 inhibited IL‐5‐mediated c‐Myc induction and promoter activity. We further examined the role of JAK1 and JAK2 in the induction of c‐Myc expression using the CDJAK fusion proteins, which consisted of a CD16 extracellular domain, a CD7 transmembrane domain, and either JAK1 (CDJAK1) or JAK2 (CDJAK2) as intracellular domains. Simultaneous activation of JAK1 and JAK2 by anti‐CD16 antibody crosslinking of CDJAK1 and CDJAK2 could induced c‐Myc expression and promoter activity; AG490 inhibited CDJAK1 and CDJAK2‐mediated effects. These results suggest that IL‐5 induces cell proliferation and anti‐apoptosis through the JAK/c‐Myc pathway, and that JAK1 and JAK2 activation participate in IL‐5‐induced up‐regulation of c‐Myc. J. Cell. Biochem. 106: 929–936, 2009. © 2009 Wiley‐Liss, Inc.