Association of Transcription Factor APRF and Protein Kinase Jak1 with the Interleukin-6 Signal Transducer gp130

TLDR

IL‑6 family cytokines bind gp130‑containing receptor complexes, rapidly inducing DNA binding of the acute‑phase response factor APRF, which is related to ISGF‑3α. Tyrosine phosphorylation of APRF, ISGF‑3α p91, and Jak family kinases, together with co‑association of APRF and Jak1 with gp130, indicates that Jak kinases participate in IL‑6 signaling and activate APRF within a gp130 complex.

Abstract

Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, interleukin-11, and ciliary neurotrophic factor bind to receptor complexes that share the signal transducer gp130. Upon binding, the ligands rapidly activate DNA binding of acute-phase response factor (APRF), a protein antigenically related to the p91 subunit of the interferon-stimulated gene factor-3 alpha (ISGF-3 alpha). These cytokines caused tyrosine phosphorylation of APRF and ISGF-3 alpha p91. Protein kinases of the Jak family were also rapidly tyrosine phosphorylated, and both APRF and Jak1 associated with gp130. These data indicate that Jak family protein kinases may participate in IL-6 signaling and that APRF may be activated in a complex with gp130.