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.


Logo for

Mol. Cell. Biol. 28 (15): 4851-4861

Copyright © 2008 by the American Society for Microbiology. All rights reserved.

How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor {alpha}{triangledown}

Erwin H. Duitman,1 Zane Orinska,1 Elena Bulanova,1 Ralf Paus,2, and Silvia Bulfone-Paus1*

Department of Immunology and Cell Biology, Research Centre Borstel, D-23845 Borstel, Germany,1 Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, D-23538 Lübeck, Germany2

Received for publication 9 December 2007. Revision received 16 February 2008. Accepted for publication 19 May 2008.

Abstract: While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor {alpha} (IL-15R{alpha}). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15R{alpha} and then is secreted. This intracellular IL-15/IL-15R{alpha} complex already is formed in the endoplasmic reticulum and, thus, enables the further trafficking of complexed IL-15 through the secretory pathway. Just transfecting IL-15R{alpha} in cells, which transcribe but normally do not secrete IL-15, suffices to induce IL-15 secretion. Thus, we provide the first evidence of how a cytokine is chaperoned through the secretory pathway by complexing with its own high-affinity receptor and show that IL-15/IL-15R{alpha} offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion.

* Corresponding author. Mailing address: Department of Immunology and Cell Biology, Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany. Phone: 49 4537 188200. Fax: 49 4537 188403. E-mail: sbulfone{at}

{triangledown} Published ahead of print on 27 May 2008.

Transcriptional Regulation of IL-15 Expression during Hematopoiesis.
S. L. Colpitts, S. W. Stonier, T. A. Stoklasek, S. H. Root, H. L. Aguila, K. S. Schluns, and L. Lefrancois (2013)
J. Immunol. 191, 3017-3024
   Abstract »    Full Text »    PDF »
Characterization and Favorable in Vivo Properties of Heterodimeric Soluble IL-15{middle dot}IL-15R{alpha} Cytokine Compared to IL-15 Monomer.
E. Chertova, C. Bergamaschi, O. Chertov, R. Sowder, J. Bear, J. D. Roser, R. K. Beach, J. D. Lifson, B. K. Felber, and G. N. Pavlakis (2013)
J. Biol. Chem. 288, 18093-18103
   Abstract »    Full Text »    PDF »
The p40 Subunit of Interleukin (IL)-12 Promotes Stabilization and Export of the p35 Subunit: IMPLICATIONS FOR IMPROVED IL-12 CYTOKINE PRODUCTION.
R. Jalah, M. Rosati, B. Ganneru, G. R. Pilkington, A. Valentin, V. Kulkarni, C. Bergamaschi, B. Chowdhury, G.-M. Zhang, R. K. Beach, et al. (2013)
J. Biol. Chem. 288, 6763-6776
   Abstract »    Full Text »    PDF »
Eosinophil crystalloid granules: structure, function, and beyond.
V. S. Muniz, P. F. Weller, and J. S. Neves (2012)
J. Leukoc. Biol. 92, 281-288
   Abstract »    Full Text »    PDF »
Circulating IL-15 exists as heterodimeric complex with soluble IL-15R{alpha} in human and mouse serum.
C. Bergamaschi, J. Bear, M. Rosati, R. K. Beach, C. Alicea, R. Sowder, E. Chertova, S. A. Rosenberg, B. K. Felber, and G. N. Pavlakis (2012)
Blood 120, e1-e8
   Abstract »    Full Text »    PDF »
Forced Homo- and Heterodimerization of All gp130-Type Receptor Complexes Leads to Constitutive Ligand-independent Signaling and Cytokine-independent Growth.
J. Suthaus, A. Tillmann, I. Lorenzen, E. Bulanova, S. Rose-John, and J. Scheller (2010)
Mol. Biol. Cell 21, 2797-2807
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Mouse Mast Cell Protease-2 by Interleukin-15.
F. Mirghomizadeh, J. Bullwinkel, Z. Orinska, O. Janssen, A. Petersen, P. B. Singh, and S. Bulfone-Paus (2009)
J. Biol. Chem. 284, 32635-32641
   Abstract »    Full Text »    PDF »
Secretion and Biological Activity of Short Signal Peptide IL-15 Is Chaperoned by IL-15 Receptor Alpha In Vivo.
C. Bergamaschi, R. Jalah, V. Kulkarni, M. Rosati, G.-M. Zhang, C. Alicea, A. S. Zolotukhin, B. K. Felber, and G. N. Pavlakis (2009)
J. Immunol. 183, 3064-3072
   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