Advertisement
JBC

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


     


Originally published In Press as doi:10.1074/jbc.M407382200 on July 16, 2004

J. Biol. Chem., Vol. 279, Issue 50, 51793-51803, December 10, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/50/51793    most recent
M407382200v1
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 Meads, M. B.
Right arrow Articles by Medveczky, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meads, M. B.
Right arrow Articles by Medveczky, P. G.
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?

Kaposi's Sarcoma-associated Herpesvirus-encoded Viral Interleukin-6 Is Secreted and Modified Differently Than Human Interleukin-6

EVIDENCE FOR A UNIQUE AUTOCRINE SIGNALING MECHANISM*

Mark B. Meads{ddagger} and Peter G. Medveczky§

Viral interleukin-6 (vIL-6) is a homolog of cellular IL-6 that is encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 binds to the IL-6 signal transducer gp130 without the cooperation of the IL-6 high affinity receptor to induce STAT3 DNA binding and cell proliferation. Although vIL-6 is believed to be important in the pathogenesis of KSHV-induced diseases, its secretion and post-translational modifications have not previously been characterized. Pulse-chase analysis revealed that the half-time of vIL-6 secretion is ~8-fold longer than that of human IL-6. Yet, the vIL-6 signal sequence targets human IL-6 secretion to nearly wild-type levels. Surprisingly, vIL-6 was not secreted from a cell line that does not express gp130 but expression of human gp130 in these cells enabled the secretion of vIL-6. Consistent with this observation, complete maturation of gp130 N-glycans is inhibited by vIL-6 coexpression, suggesting that the binding of the receptor to vIL-6 occurs intracellularly in early or pre-Golgi compartments. Furthermore, a vIL-6 mutant containing an endoplasmic reticulum retention signal is not secreted but does still induce receptor activation and signaling. Secreted vIL-6 is completely glycosylated at both possible N-glycosylaton sites and contains a large proportion of immature high-mannose glycans that is not typical of cytokines. These findings suggest that vIL-6 may induce gp130 signaling by an exclusively autocrine mechanism that relies on intracellular binding to its receptor. During KSHV infection, vIL-6 may only induce signaling in KSHV-infected cells to benefit the viral life cycle and promote oncogenic transformation.


Received for publication, July 1, 2004

* This work was supported by Grant 1R01CA75894 from the National Institutes of Health (to P. G. M.). 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.

{ddagger} Supported by Training Grant T32DA07245 from the National Institutes of Health.

§ To whom correspondence should be addressed. Tel.: 813-974-2372; Fax: 813-974-4151; E-mail: pmedvecz{at}hsc.usf.edu.


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. Virol.Home page
D. Chen, Y. B. Choi, G. Sandford, and J. Nicholas
Determinants of Secretion and Intracellular Localization of Human Herpesvirus 8 Interleukin-6
J. Virol., July 1, 2009; 83(13): 6874 - 6882.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
N. Adam, B. Rabe, J. Suthaus, J. Grotzinger, S. Rose-John, and J. Scheller
Unraveling Viral Interleukin-6 Binding to gp130 and Activation of STAT-Signaling Pathways Independently of the Interleukin-6 Receptor
J. Virol., May 15, 2009; 83(10): 5117 - 5126.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
D. Chen, G. Sandford, and J. Nicholas
Intracellular Signaling Mechanisms and Activities of Human Herpesvirus 8 Interleukin-6
J. Virol., January 15, 2009; 83(2): 722 - 733.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
P. Gasperini, S. Sakakibara, and G. Tosato
Contribution of viral and cellular cytokines to Kaposi's sarcoma-associated herpesvirus pathogenesis
J. Leukoc. Biol., October 1, 2008; 84(4): 994 - 1000.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
M. de Turenne-Tessier and T. Ooka
Post-translational modifications of Epstein Barr virus BARF1 oncogene-encoded polypeptide
J. Gen. Virol., October 1, 2007; 88(10): 2656 - 2661.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
F.-C. Ye, D. J. Blackbourn, M. Mengel, J.-P. Xie, L.-W. Qian, W. Greene, I-T. Yeh, D. Graham, and S.-J. Gao
Kaposi's Sarcoma-Associated Herpesvirus Promotes Angiogenesis by Inducing Angiopoietin-2 Expression via AP-1 and Ets1
J. Virol., April 15, 2007; 81(8): 3980 - 3991.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
D. Chen and J. Nicholas
Structural Requirements for gp80 Independence of Human Herpesvirus 8 Interleukin-6 (vIL-6) and Evidence for gp80 Stabilization of gp130 Signaling Complexes Induced by vIL-6
J. Virol., October 1, 2006; 80(19): 9811 - 9821.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
M. Kovaleva, I. Bussmeyer, B. Rabe, J. Grotzinger, E. Sudarman, J. Eichler, U. Conrad, S. Rose-John, and J. Scheller
Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display.
J. Virol., September 1, 2006; 80(17): 8510 - 8520.
[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 © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement