TY - JOUR
T1 - Identification of amino acid residues of gp130 signal transducer and gp80 α receptor subunit that are involved in ligand binding and signaling by human herpesvirus 8-encoded interleukin-6
AU - Li, Hong
AU - Nicholas, John
PY - 2002
Y1 - 2002
N2 - Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp13O signal transducer but is not dependent on the IL-6 receptor α subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R can enhance vIL-6 activity and can enable signaling through a gp130 variant, gp130.PM5, that is itself unable to support vIL-6 signaling. These findings suggest that the vIL-6-gp130 interactions are qualitatively different from those of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine the receptor binding requirements of vIL-6, we have undertaken mutational analyses of regions of gp130 and IL-6R potentially involved in interactions with ligand or in functional complex formation and used these variants in functional, ligand-binding, and receptor dimerization assays. The data presented identify positions within two interstrand loops of the gp130 cytokine-receptor homology domain that are important for vIL-6 signaling and vIL-6-induced receptor dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand-induced functional complex formation are qualitatively different in the case of vIL-6 and hIL-6.
AB - Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp13O signal transducer but is not dependent on the IL-6 receptor α subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R can enhance vIL-6 activity and can enable signaling through a gp130 variant, gp130.PM5, that is itself unable to support vIL-6 signaling. These findings suggest that the vIL-6-gp130 interactions are qualitatively different from those of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine the receptor binding requirements of vIL-6, we have undertaken mutational analyses of regions of gp130 and IL-6R potentially involved in interactions with ligand or in functional complex formation and used these variants in functional, ligand-binding, and receptor dimerization assays. The data presented identify positions within two interstrand loops of the gp130 cytokine-receptor homology domain that are important for vIL-6 signaling and vIL-6-induced receptor dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand-induced functional complex formation are qualitatively different in the case of vIL-6 and hIL-6.
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U2 - 10.1128/JVI.76.11.5627-5636.2002
DO - 10.1128/JVI.76.11.5627-5636.2002
M3 - Article
C2 - 11991991
AN - SCOPUS:0036091823
SN - 0022-538X
VL - 76
SP - 5627
EP - 5636
JO - Journal of virology
JF - Journal of virology
IS - 11
ER -