fig3

Figure 3. Multiple signaling cascades are activated following IL-6 binding to its receptor (GP130). Ligand binding causes GP130 dimerization and activation (phosphorylation) of the associated JAK kinase, which then activates downstream STAT transcription factor. GP130 activation can also transduce second messenger signaling via the RAS/RAF/MEK/ERK pathway to activate MAP kinase (MAPK). In addition, this inflammatory cytokine can also initiate the PI3K signaling at the membrane, which can either activate IκB kinase (IKK) and thus enhance NF-κB transcription factor function or PI3K may activate the downstream protein kinase B (AKT) which suppress NF-κB activation. Therefore, IL-6 signaling activates multiple redox signaling networks that may crosstalk with AR and activate it in a ligand-independent manner. IL-6: interleukin-6; JAK: Janus associated kinase; STAT: signal transducers and activators of transcription; NF-κB: nuclear factor kappa B