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. 2023 Dec 1;14(6):2113–2126. doi: 10.14336/AD.2023.0306

Figure 1.

Figure 1.

The signaling pathway downstream of IL-11/IL-11R. In classic signaling, IL-11 binds to the unique receptor IL-11Rα and signal-transducing receptor gp130. The IL-11/IL-11R complex recruits a homodimer of the signal-transducing receptor gp130, resulting in activation of downstream signaling. In trans-signaling, the gp130 dimer is induced by IL-11 bound to the soluble IL-11R (sIL-11R). After IL-11 binds to receptors, JAKs forms a complex with the adapter protein. The STATs then become tyrosine phosphorylated and translocates into the nucleus and trigger the transcriptional modulation of target genes. IL-11 drives non-canonical ERK-dependent autocrine signaling for fibrogenic protein synthesis, then promotes the formation of the active Grb2/SOS complex, then phosphorylate MEK kinases, and results in MAPK activation. IL-11 can also activate the PI3K/AKT pathway, independent of the tyrosine-phosphorylation of gp130, in tumor metastasis. The downstream signaling cascades are activated, including JAK/STAT1/STAT3, PI3K/Akt, and Ras/Raf/MAPK signaling in physiological and pathological condition, to promote target gene transcription.