Figure 1: Activation of JAK/STAT by IL-6. The membrane-bound IL-6R (mIL-6R) pathway (far left), canonical IL-6/IL-6R/gp130 pathway (middle), and “non-canonical” IL-6 trans -signaling pathway (far right) is shown where IL-6 interacts with sIL-6R. The canonical IL-6/IL-6R/gp130 pathway is known to activate JAK/ STAT and SAPK/MAPK signaling [3]. The JAK/STAT pathway activated by IL-6/IL-6R/gp130 may also activate the SAPK/MAPK pathway via a “cross-talk” mechanism (→?→) [3]. JAK/STAT could also be activated by IL-6 via mIL-6R in cells lacking the gp130 subunit [53]. Under these conditions activated STAT proteins may also initiate SAPK/MAPK signaling (↓?).