Fig. 2
From: Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6
IL-6 classical and trans-signaling pathways. a IL-6 binds to cells that express both the membrane bound IL-6R gp130 and trigger the activation of the JAK/STAT signaling pathway. This type of signaling is called classical signaling. b In cells that express only gp130 but not IL-6R, IL-6 binds to soluble IL-6R (sIL-6R) and the complex in turn bind to gp130 to trigger the activation of intracellular signaling. This type of signaling is called trans-signaling. The sIL-6R is released by proteolytic cleavage of the IL-6R membrane bound precursor by the metalloproteases ADAM10 and 17. A natural form of gp130 is able to bind to the sIL-6R bound to IL-6 with comparable affinity and mediates inhibition of IL-6 trans-signaling