Figure 1. Schematic of the cytoplasmic regions of human gp130 and LIFR showing the relative locations of the three box motifs and the STAT3 YXXQ binding motifs. The YXXV domain is important for linking the receptors to PI3K/AKT and SHP2/MAPK signaling pathways and for termination of signaling by recruiting either SHP2 or SOCS3. SHP2 terminates signaling through its tyrosine phosphatase activity. SOCS3 terminates signaling by inhibiting JAK activity directly through the N-terminal kinase inhibitory region (KIR) or by facilitating the ubiquitination and proteasomal degradation of signaling components.