Figure 2. Diagrammatic representation of interactions between leptin (Lep) and insulin (Ins) signal transduction pathways.
P = phosphorylation events. The three pathways discussed (MAPK/ERK, STAT3, PI3K/PKB) are highlighted in blue. The Jak/STAT3 pathway is the best characterized; LepR mediates signalling via the receptor-associated Jak2 tyrosine kinase, which phosphorylates the tyrosine residue Tyr1138 on the intracellular tail of the LepR. Phosphorylation of Tyr1138 recruits the cytoplasmic transcription factor STAT3, which is phosphorylated by Jak2. Phosphorylated STAT3 molecules form dimers, and translocate into the nucleus to activate gene transcription. Note, leptin can activate all three pathways, and recent work suggests that the PKB pathway is required for STAT-mediated signalling, possibly by phosphorylating and thereby inactivating FOXO1, which can otherwise act to inhibit STAT-mediated gene transcription.