FIGURE 7.

Mannose phosphorylation controls LIF extracellular levels by multiple mechanisms. In WT cells, mannose phosphorylation and subsequent lysosomal trafficking of newly synthesized LIF can limit its secretion, and uptake of secreted LIF via cell surface CI-MPR can also help to reduce its extracellular levels. In ML-II cells, loss of GlcNAc-1-phosphotransferase activity and impaired mannose phosphorylation of proteins will “unhinge” these control mechanisms leading to accumulation of extracellular LIF and increased LIF signaling and activity.