Figure 3. Schematic diagram of signal transduction pathways induced by leptin in the clonal, hypothalamic NT cell model, N-39. In N-39, we provide evidence for activation of three specific signal transduction pathways by leptin, all dependent on JAK2 signaling. ERK1/2 and p38 are induced by leptin receptor activation. STAT3 is also involved in leptin-mediated regulation of NT/N gene expression; we describe its binding to the mouse NT/N promoter region. We describe the involvement of downstream activators c-Fos and ATF-1, and speculate that JAK/STAT and p38 MAPK pathways are predominant at physiological leptin levels whereas the ERK1/2 MAPK pathway may be utilized more prominently at higher leptin concentrations.