PMID: 14970177

 

    Legend: Sugar

Title : N-linked glycosylation is required for optimal function of Kaposi's sarcoma herpesvirus-encoded, but not cellular, interleukin 6

Abstract :

1. Kaposi's sarcoma-associated herpesvirus interleukin-6 ( vIL-6) is a structural and functional homologue of the human cytokine IL-6 ( hIL-6 )
2. 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
3. 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
4. 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 alpha-dependent binding to gp130 or signaling through JAK1- STAT1 /3
5. As distinct from vIL-6, unglycosylated hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation
6. These findings highlight distinct functional roles of N-linked glycosylation in viral and cellular IL-6