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

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...

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Main Authors:	Nagy, Zsuzsanna S., Ross, Jeremy A., Rodriguez, Georgialina, Balint, Balint L., Szeles, Lajos, Nagy, Laszlo, Kirken, Robert A.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581501/

id	pubmed-3581501
recordtype	oai_dc
spelling	pubmed-35815012013-02-28 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. Szeles, Lajos Nagy, Laszlo Kirken, Robert A. Research Article 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. Public Library of Science 2013-02-25 /pmc/articles/PMC3581501/ /pubmed/23451206 http://dx.doi.org/10.1371/journal.pone.0057326 Text en © 2013 Nagy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Nagy, Zsuzsanna S. Ross, Jeremy A. Rodriguez, Georgialina Balint, Balint L. Szeles, Lajos Nagy, Laszlo Kirken, Robert A.
spellingShingle	Nagy, Zsuzsanna S. Ross, Jeremy A. Rodriguez, Georgialina Balint, Balint L. Szeles, Lajos Nagy, Laszlo Kirken, Robert A. Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
author_facet	Nagy, Zsuzsanna S. Ross, Jeremy A. Rodriguez, Georgialina Balint, Balint L. Szeles, Lajos Nagy, Laszlo Kirken, Robert A.
author_sort	Nagy, Zsuzsanna S.
title	Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
title_short	Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
title_full	Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
title_fullStr	Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
title_full_unstemmed	Genome Wide Mapping Reveals PDE4B as an IL-2 Induced STAT5 Target Gene in Activated Human PBMCs and Lymphoid Cancer Cells
title_sort	genome wide mapping reveals pde4b as an il-2 induced stat5 target gene in activated human pbmcs and lymphoid cancer cells
description	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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581501/
_version_	1611957415572406272

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

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