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(A). Classic IL-6 signaling: IL-6 binds with the cytokine-binding domain of the extracellular portion of mIL-6R, signaling gp130 to activate Janus kinase (JAK). (B). Trans IL-6 signaling: the cleaved extracellular portion of mIL-6 and the cytokine-binding domain form the sIL-6R. The complex formed by sIL-6R and IL-6 will signal gp130 to activate Janus kinase (JAK).
