Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 23 December 2008
Vol. 1, Issue 51, p. pe55
[DOI: 10.1126/scisignal.1.51.pe55]


Untangling the Complex Web of IL-4– and IL-13–Mediated Signaling Pathways

Marsha Wills-Karp1* and Fred D. Finkelman1,2

1 Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA.
2 Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0555, USA, and Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.

Abstract: Unraveling the exact signaling events mediating the distinct functions of the T cell–derived cytokines interleukin-4 (IL-4) and IL-13 has been challenging because they are structurally similar and share a functional signaling receptor chain. A study now proposes a potential molecular mechanism to explain the functional differences between IL-4 and IL-13 that involves the ability of IL-4, but not IL-13, to effectively activate the insulin receptor substrate–2 (IRS-2) signaling cascade through binding to its receptor. A better understanding of the interactions of IL-4 and IL-13 with their cognate receptors may facilitate the development of therapies without unintended side effects.

* Corresponding author. E-mail, wildc7{at}

Citation: M. Wills-Karp, F. D. Finkelman, Untangling the Complex Web of IL-4– and IL-13–Mediated Signaling Pathways. Sci. Signal. 1, pe55 (2008).

Read the Full Text

A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1.
M. Gauthier, A. Marteyn, J. A. Denis, M. Cailleret, K. Giraud-Triboult, S. Aubert, C. Lecuyer, J. Marie, D. Furling, R. Vernet, et al. (2013)
Hum. Mol. Genet. 22, 5188-5198
   Abstract »    Full Text »    PDF »
Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK.
H. D. Kim, S.-J. Yu, H. S. Kim, Y.-J. Kim, J. M. Choe, Y. G. Park, J. Kim, and J. Sohn (2013)
J. Biol. Chem. 288, 28743-28754
   Abstract »    Full Text »    PDF »
Endoplasmic reticulum stress impairs IL-4/IL-13 signaling through C/EBP{beta}-mediated transcriptional suppression.
A. M. Arensdorf and D. Thomas Rutkowski (2013)
J. Cell Sci. 126, 4026-4036
   Abstract »    Full Text »    PDF »
Differential effects of {gamma}c cytokines on postselection differentiation of CD8 thymocytes.
M. Rafei, A. Rouette, S. Brochu, J. R. Vanegas, and C. Perreault (2013)
Blood 121, 107-117
   Abstract »    Full Text »    PDF »
Cytokine Stimulation of Epithelial Cancer Cells: The Similar and Divergent Functions of IL-4 and IL-13.
M. A. Hallett, K. T. Venmar, and B. Fingleton (2012)
Cancer Res. 72, 6338-6343
   Abstract »    Full Text »    PDF »
Polymorphisms in the IL-13 and IL-4R genes are associated with the development of renal cell carcinoma.
H. Chu, M. Wang, F. Yan, D. Zhong, D. Shi, L. Ma, X. Pan, C. Qin, C. Yin, and Z. Zhang (2012)
Ann. Onc. 23, 2114-2121
   Abstract »    Full Text »    PDF »
Aptamer-Mediated Blockade of IL4R{alpha} Triggers Apoptosis of MDSCs and Limits Tumor Progression.
F. Roth, A. C. De La Fuente, J. L. Vella, A. Zoso, L. Inverardi, and P. Serafini (2012)
Cancer Res. 72, 1373-1383
   Abstract »    Full Text »    PDF »
Non-canonical alternatives: What a macrophage is 4.
C. L. Karp and P. J. Murray (2012)
J. Exp. Med. 209, 427-431
   Abstract »    Full Text »    PDF »
Development and Function of Innate Polyclonal TCR{alpha}{beta}+ CD8+ Thymocytes.
M. Rafei, M.-P. Hardy, P. Williams, J. R. Vanegas, K.-A. Forner, G. Dulude, N. Labrecque, J. Galipeau, and C. Perreault (2011)
J. Immunol. 187, 3133-3144
   Abstract »    Full Text »    PDF »
Hierarchical IL-5 Expression Defines a Subpopulation of Highly Differentiated Human Th2 Cells.
B. Upadhyaya, Y. Yin, B. J. Hill, D. C. Douek, and C. Prussin (2011)
J. Immunol. 187, 3111-3120
   Abstract »    Full Text »    PDF »
5A, an Apolipoprotein A-I Mimetic Peptide, Attenuates the Induction of House Dust Mite-Induced Asthma.
X. Yao, C. Dai, K. Fredriksson, P. K. Dagur, J. P. McCoy, X. Qu, Z.-X. Yu, K. J. Keeran, G. J. Zywicke, M. J. A. Amar, et al. (2011)
J. Immunol. 186, 576-583
   Abstract »    Full Text »    PDF »
Foxa2 Programs Th2 Cell-Mediated Innate Immunity in the Developing Lung.
G. Chen, H. Wan, F. Luo, L. Zhang, Y. Xu, I. Lewkowich, M. Wills-Karp, and J. A. Whitsett (2010)
J. Immunol. 184, 6133-6141
   Abstract »    Full Text »    PDF »
IL-4 and TGF-{beta}1 Counterbalance One Another while Regulating Mast Cell Homeostasis.
M. R. Macey, J. L. Sturgill, J. K. Morales, Y. T. Falanga, J. Morales, S. K. Norton, N. Yerram, H. Shim, J. Fernando, A. M. Gifillan, et al. (2010)
J. Immunol. 184, 4688-4695
   Abstract »    Full Text »    PDF »
Establishment of Extracellular Signal-Regulated Kinase 1/2 Bistability and Sustained Activation through Sprouty 2 and Its Relevance for Epithelial Function.
W. Liu, K. Tundwal, Q. Liang, N. Goplen, S. Rozario, N. Quayum, M. Gorska, S. Wenzel, S. Balzar, and R. Alam (2010)
Mol. Cell. Biol. 30, 1783-1799
   Abstract »    Full Text »    PDF »
Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma.
C. K. Oh, G. P. Geba, and N. Molfino (2010)
Eur. Respir. Rev. 19, 46-54
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882