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

Wei Hwa Lee, Fu Hwa Liu, John Yi Chung Lin, Shih Yun Huang, Heng Lin, Wei Ju Liao, Huei Mei Huang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFa1 and TFa8 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.

Original languageEnglish
Pages (from-to)929-936
Number of pages8
JournalJournal of Cellular Biochemistry
Volume106
Issue number5
DOIs
Publication statusPublished - Apr 1 2009
Externally publishedYes

Fingerprint

Interleukin-5
Cell proliferation
Cell Proliferation
Apoptosis
Interleukin-5 Receptors
Up-Regulation
Chemical activation
STAT5 Transcription Factor
Proto-Oncogene Proteins c-myc
Janus Kinases
Hematopoietic Stem Cells
Crosslinking
Anti-Idiotypic Antibodies
Proteins
Fusion reactions
Cells
RNA
Cell Line
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
Antibodies

Keywords

  • Anti-apoptosis
  • C-Myc
  • Cell proliferation
  • IL-5
  • JAK

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis. / Lee, Wei Hwa; Liu, Fu Hwa; Lin, John Yi Chung; Huang, Shih Yun; Lin, Heng; Liao, Wei Ju; Huang, Huei Mei.

In: Journal of Cellular Biochemistry, Vol. 106, No. 5, 01.04.2009, p. 929-936.

Research output: Contribution to journalArticle

@article{a07413479c434928890f8da89d4ac975,
title = "JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis",
abstract = "Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFa1 and TFa8 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.",
keywords = "Anti-apoptosis, C-Myc, Cell proliferation, IL-5, JAK",
author = "Lee, {Wei Hwa} and Liu, {Fu Hwa} and Lin, {John Yi Chung} and Huang, {Shih Yun} and Heng Lin and Liao, {Wei Ju} and Huang, {Huei Mei}",
year = "2009",
month = "4",
day = "1",
doi = "10.1002/jcb.22069",
language = "English",
volume = "106",
pages = "929--936",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis

AU - Lee, Wei Hwa

AU - Liu, Fu Hwa

AU - Lin, John Yi Chung

AU - Huang, Shih Yun

AU - Lin, Heng

AU - Liao, Wei Ju

AU - Huang, Huei Mei

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFa1 and TFa8 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.

AB - Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFa1 and TFa8 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.

KW - Anti-apoptosis

KW - C-Myc

KW - Cell proliferation

KW - IL-5

KW - JAK

UR - http://www.scopus.com/inward/record.url?scp=65349187559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65349187559&partnerID=8YFLogxK

U2 - 10.1002/jcb.22069

DO - 10.1002/jcb.22069

M3 - Article

C2 - 19180571

AN - SCOPUS:65349187559

VL - 106

SP - 929

EP - 936

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 5

ER -