Evidence map›Paper›PMID 19109239›Full record

ArticleScience signaling2008

Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages.

Nicola M Heller, Xiulan Qi, Ilkka S Junttila, Kari Ann Shirey, Stefanie N Vogel, William E Paul, Achsah D Keegan

Abstract read
In one paragraph

Article in Science signaling, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 156 citations in OpenAlex.

  1. Article
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  5. Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  17. Tumor-Associated Macrophage Subsets: Shaping Polarization and Targeting.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Article
  20. Article

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Nicola M HellerCenter for Vascular and Inflammatory Diseases, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Xiulan Qi
Ilkka S Junttila
Kari Ann Shirey
Stefanie N Vogel
William E Paul
Achsah D Keegan
University of Maryland, Baltimore · USNational Institute of Allergy and Infectious Diseases · US

Funding

Interleukin 4ZIAAI000493 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GERMAIN, RONALD N · 2009 to 2017
$11.5M
Vascular Biology Training ProgramT32HL007698 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Rosemary A Kozar, Dudley K. Strickland · 1991 to 2026
$8.7M
DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATIONR37AI018797 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI VOGEL, STEFANIE N. · 2000 to 2009
$5.3M
DIFFERENTIATIVE SIGNALS FOR MACROPHANGE ACTIVATIONR01AI018797 · NIAID · U.S. UNIFORMED SERVICES UNIV OF HLTH SCI · PI VOGEL, STEFANIE N. · 1985 to 2014
$3.8M
Molecular Mechanisms of IL-4 and IL-13 SignalingR01AI038985 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI KEEGAN, ACHSAH D. · 2001 to 2010
$3.7M
Regulation of Myeloid Development and Function by II-4R01AI059775 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI KEEGAN, ACHSAH D. · 2005 to 2010
$1.7M
Differentiative Signals for Macrophage ActivationR56AI018797 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI VOGEL, STEFANIE N. · 2015 to 2015
$506k
MOLECULAR MECHANISM OF IL4 SIGNALINGR29AI038985 · NIAID · AMERICAN NATIONAL RED CROSS · PI KEEGAN, ACHSAH D. · 1996 to 2000
$96k
NHLBI NIH HHS T32 HL 007698NHLBI NIH HHS T32 HL007698NIAID NIH HHS AI 018797NIAID NIH HHS AI 038985NIAID NIH HHS AI 059775NIAID NIH HHS R01 AI038985NIAID NIH HHS R01 AI059775NIAID NIH HHS R37 AI018797
6 · The paper itself

Abstract

Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and share a receptor subunit (IL-4Ralpha), they have different functions. We compared cells expressing type I and II IL-4Rs with cells expressing only type II receptors for their responsiveness to these cytokines. IL-4 induced highly efficient, gammaC-dependent tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2), whereas IL-13 was less effective, even when phosphorylation of signal transducer and activator of transcription 6 (STAT6) was maximal. Only type I receptor, gammaC-dependent signaling induced efficient association of IRS-2 with the p85 subunit of phosphoinositide 3-kinase or the adaptor protein growth factor receptor-bound protein 2. In addition, IL-4 signaling through type I IL-4Rs induced more robust expression of a subset of genes associated with alternatively activated macrophages than did IL-13. Thus, IL-4 activates signaling pathways through type I IL-4Rs qualitatively differently from IL-13, which cooperate to induce optimal gene expression.

Indexed as

Transcriptional ActivationCell LineHumansInsulin Receptor Substrate ProteinsInterleukin-13MacrophagesPhosphorylationReceptors, Interleukin-4, Type ISignal TransductionSTAT6 Transcription FactorInsulin Receptor Substrate ProteinsInterleukin-13Receptors, Interleukin-4, Type ISTAT6 Transcription Factor

Identifiers

PMID19109239
PMCPMC2739727
OpenAlexW2136677567

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.