Trans-signaling of interleukin-6 (IL-6) is mediated by the soluble IL-6 receptor, but not by soluble CD5.

IL-6 exerts its pleiotropic activities on its target cells via the IL-6 alpha-receptor (IL-6R), which is expressed on a limited number of cell types. IL-6 can further signal via soluble forms of its receptor (sIL-6R), a process that has been termed trans-signaling. Recently, CD5 was described as an alternative alpha-receptor for IL-6 on B cells leading to the phosphorylation of the transcription factor STAT3 via the signal-transducing β-receptor gp130 in a Jak2-dependent manner.

Oncogenic deletion mutants of gp130 signal from intracellular compartments.

Interleukin 6 (IL-6) and, hence, activation of the IL-6 receptor signalling subunit glycoprotein 130 (gp130; also known as interleukin-6 receptor subunit β, IL6ST), has been linked to inflammation and tumour formation. Recently, deletion mutations in gp130 have been identified in inflammatory hepatocellular adenoma. The mutations clustered around one IL-6-binding epitope and rendered gp130 constitutively active in a ligand-independent manner.