Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M610036200 on February 27, 2007

J. Biol. Chem., Vol. 282, Issue 18, 13167-13179, May 4, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
282/18/13167    most recent
M610036200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bulanova, E.
Right arrow Articles by Bulfone-Paus, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bulanova, E.
Right arrow Articles by Bulfone-Paus, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Soluble Interleukin (IL)-15R{alpha} Is Generated by Alternative Splicing or Proteolytic Cleavage and Forms Functional Complexes with IL-15*

Elena Bulanova{ddagger}1, Vadim Budagian{ddagger}, Erwin Duitman{ddagger}, Zane Orinska{ddagger}, Hans Krause§, Rene Rückert{ddagger}, Norbert Reiling, and Silvia Bulfone-Paus{ddagger}

From the Departments of {ddagger}Immunology and Cell Biology and Immunochemistry and Biochemical Microbiology, Research Center Borstel, Borstel D-23845, Germany and the §Department of Urology, Charité University Medicine, Campus Benjamin Franklin, Berlin D-12200, Germany

Interleukin 15 (IL-15) is a pleiotropic cytokine that is hardly detectable in biological fluids. Here, we show that IL-15 forms functional heterocomplexes with soluble high affinity IL-15 receptor {alpha} (IL-15R{alpha}) chain in mouse serum and cell-conditioned medium, which prevents IL-15 detection by ELISA. We also demonstrate that two soluble IL-15R{alpha} (sIL-15R{alpha}) sushi domain isoforms are generated through a novel alternative splicing mechanism within the IL-15R{alpha} gene. These isoforms potentiate IL-15 action by promoting the IL-15-mediated proliferation of the CTLL cell line and interferon {gamma} production by murine NK cells, which suggests a role in IL-15 transpresentation. Conversely, a full-length sIL-15R{alpha} ectodomain released by tumor necrosis factor-{alpha}-converting enzyme (TACE)-dependent proteolysis inhibits IL-15 activity. Thus, a dual mechanism of sIL-15R{alpha} generation exists in mice, giving rise to polypeptides with distinct properties, which regulate IL-15 function.

Received for publication, October 26, 2006 , and in revised form, February 12, 2007.

* This work was supported by Deutsche Forschungsgemeinschaft Grant SFB415, A10 (to S. B. P. and E. B.) and an autoimmunity research grant from Lübeck University (Teilproject A2) (to E. B. and S. B. P). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed. Tel.: 49-4537188564; Fax: 49-4537188403; E-mail: ebulanova{at}fz-borstel.de.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A.-H. Pillet, F. Bugault, J. Theze, L. A. Chakrabarti, and T. Rose
A Programmed Switch from IL-15- to IL-2-Dependent Activation in Human NK Cells
J. Immunol., May 15, 2009; 182(10): 6267 - 6277.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Giron-Michel, F. Menard, S. Negrini, A. Devocelle, B. Azzarone, and C. Besson
EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15
Blood, May 7, 2009; 113(19): 4541 - 4547.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Zhang, Z. Yao, S. Dubois, W. Ju, J. R. Muller, and T. A. Waldmann
Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer
PNAS, May 5, 2009; 106(18): 7513 - 7518.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Khawam, J. Giron-Michel, Y. Gu, A. Perier, M. Giuliani, A. Caignard, A. Devocelle, S. Ferrini, M. Fabbi, B. Charpentier, et al.
Human Renal Cancer Cells Express a Novel Membrane-Bound Interleukin-15 that Induces, in Response to the Soluble Interleukin-15 Receptor {alpha} Chain, Epithelial-to-Mesenchymal Transition
Cancer Res., February 15, 2009; 69(4): 1561 - 1569.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
L. S. Quinn, B. G. Anderson, L. Strait-Bodey, A. M. Stroud, and J. M. Argiles
Oversecretion of interleukin-15 from skeletal muscle reduces adiposity
Am J Physiol Endocrinol Metab, January 1, 2009; 296(1): E191 - E202.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z. Wu, H.-H. Xue, J. Bernard, R. Zeng, D. Issakov, J. Bollenbacher-Reilley, I. M. Belyakov, S. Oh, J. A. Berzofsky, and W. J. Leonard
The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15R{alpha} function but is not required for trans-presentation
Blood, December 1, 2008; 112(12): 4411 - 4419.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Y. Tiao, A. Bradaia, B. Biermann, K. Kaupmann, M. Metz, C. Haller, A. G. Rolink, E. Pless, P. N. Barlow, M. Gassmann, et al.
The Sushi Domains of Secreted GABAB1 Isoforms Selectively Impair GABAB Heteroreceptor Function
J. Biol. Chem., November 7, 2008; 283(45): 31005 - 31011.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. H. Duitman, Z. Orinska, E. Bulanova, R. Paus, and S. Bulfone-Paus
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}
Mol. Cell. Biol., August 1, 2008; 28(15): 4851 - 4861.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Ullrich, M. Bonmort, G. Mignot, B. Jacobs, D. Bosisio, S. Sozzani, A. Jalil, F. Louache, E. Bulanova, F. Geissman, et al.
Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions
J. Immunol., June 15, 2008; 180(12): 7887 - 7897.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. J. Levine
Molecular Mechanisms of Soluble Cytokine Receptor Generation
J. Biol. Chem., May 23, 2008; 283(21): 14177 - 14181.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Badoual, G. Bouchaud, N. E. H. Agueznay, E. Mortier, S. Hans, A. Gey, F. Fernani, S. Peyrard, P. L. -Puig, P. Bruneval, et al.
The Soluble {alpha} Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer
Cancer Res., May 15, 2008; 68(10): 3907 - 3914.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
L. S. Quinn
Interleukin-15: A muscle-derived cytokine regulating fat-to-lean body composition
J Anim Sci, April 1, 2008; 86(14_suppl): E75 - E83.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Bergamaschi, M. Rosati, R. Jalah, A. Valentin, V. Kulkarni, C. Alicea, G.-M. Zhang, V. Patel, B. K. Felber, and G. N. Pavlakis
Intracellular Interaction of Interleukin-15 with Its Receptor {alpha} during Production Leads to Mutual Stabilization and Increased Bioactivity
J. Biol. Chem., February 15, 2008; 283(7): 4189 - 4199.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Olsen, N. Ota, S. Kishishita, M. Kukimoto-Niino, K. Murayama, H. Uchiyama, M. Toyama, T. Terada, M. Shirouzu, O. Kanagawa, et al.
Crystal Structure of the Interleukin-15{middle dot}Interleukin-15 Receptor {alpha} Complex: INSIGHTS INTO TRANS AND CIS PRESENTATION
J. Biol. Chem., December 21, 2007; 282(51): 37191 - 37204.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J.-H. Cho, O. Boyman, H.-O. Kim, B. Hahm, M. P. Rubinstein, C. Ramsey, D. M. Kim, C. D. Surh, and J. Sprent
An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2
J. Exp. Med., August 6, 2007; 204(8): 1787 - 1801.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement