|
|
|
|
|
|
|
||
Address correspondence to George Miller, Department of Pediatrics, Yale University School of Medicine, Room 420 LSOG, 333 Cedar Street, New Haven, CT 06520. Phone: (203) 785-4758; Fax: (203) 785-6961; email: George.Miller{at}Yale.edu
Kaposi's sarcoma–associated herpesvirus interleukin-6 (vIL-6) is a structural and functional homologue of the human cytokine IL-6 (hIL-6). hIL-6 and vIL-6 exhibit similar biological functions and both act via the gp130 receptor subunit to activate the Janus tyrosine kinase (JAK)1 and signal transducer and activator of transcription (STAT)1/3 pathway. Here we show that vIL-6 is N-linked glycosylated at N78 and N89 and demonstrate that N-linked glycosylation at site N89 of vIL-6 markedly enhances binding to gp130, signaling through the JAK1-STAT1/3 pathway and functions in a cytokine-dependent cell proliferation bioassay. Although hIL-6 is also N-glycosylated at N73 and multiply O-glycosylated, neither N-linked nor O-linked glycosylation is necessary for IL-6 receptor
–dependent binding to gp130 or signaling through JAK1-STAT1/3. As distinct from vIL-6, unglycosylated hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation. These findings highlight distinct functional roles of N-linked glycosylation in viral and cellular IL-6.
Key Words: IL-6 • viral proteins • glycosylation • KSHV • cytokine
Abbreviations used in this paper: hIL-6, human IL-6; HRP, horseradish peroxidase; JAK, Janus tyrosine kinase; KSHV, Kaposi's sarcoma–associated herpesvirus; PEL, primary effusion lymphoma; STAT, signal transducer and activator of transcription; TM, tunicamycin; vIL-6, viral IL-6.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
