Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells

Zsuzsanna S. Nagy, Jeremy A. Ross, Georgialina Rodriguez, Balint L. Balint, L. Széles, L. Nagy, Robert A. Kirken

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B (commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoid tumor cells, suggesting that it and its target genes represent therapeutic targets to control certain lymphoid diseases. To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225. Select overlapping genes were then validated using qRT2PCR medium-throughput arrays in human PHA-activated PBMCs. Of 19 putative genes, one key regulator of T cell receptor signaling, PDE4B, was identified as a novel target, which was readily up-regulated at the protein level (3 h) in IL-2 stimulated, activated human PBMCs. Surprisingly, only purified CD8+ primary T-cells expressed PDE4B, but not CD4+ cells. Moreover, PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for pharmaceutical intervention for certain lymphoid diseases.

Original languageEnglish
Article numbere57326
JournalPLoS One
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 25 2013

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Chromosome Mapping
mononuclear leukocytes
interleukin-2
Interleukin-2
Genes
Cells
T-cells
Lymphocytes
T-lymphocytes
genome
T-Lymphocytes
Neoplasms
Janus Kinase 3
Janus Kinase 1
genes
Overlapping Genes
STAT5 Transcription Factor
cdc Genes
non-specific protein-tyrosine kinase
T-Cell Antigen Receptor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells. / Nagy, Zsuzsanna S.; Ross, Jeremy A.; Rodriguez, Georgialina; Balint, Balint L.; Széles, L.; Nagy, L.; Kirken, Robert A.

In: PLoS One, Vol. 8, No. 2, e57326, 25.02.2013.

Research output: Contribution to journalArticle

Nagy, Zsuzsanna S. ; Ross, Jeremy A. ; Rodriguez, Georgialina ; Balint, Balint L. ; Széles, L. ; Nagy, L. ; Kirken, Robert A. / Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells. In: PLoS One. 2013 ; Vol. 8, No. 2.
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