Figures
- FIGURE 1
Leptin receptor and intracellular leptin signalling pathways. Leptin binds to LepRb causing dimerisation and phosphorylation of Janus kinase 2 (JAK2) and tyrosine residues within LepRb. Activation of JAK2 initiates three signalling pathways. 1) JAK2/signal transducer and activator of transcription 3 (STAT3) pathway: LepRb phosphorylated Tyr1138 mediates the dimerisation and translocation of STAT3 into the nucleus to activate gene transcription. Suppressor of cytokine signalling 3 (SOCS3) acts as a negative feedback mechanism during prolonged stimulation of LepRb. 2) Mitogen-activated protein kinase (MAPK) pathway: leptin induces the activation of Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2), which recruits the adaptor protein growth factor receptor-bound protein 2 (GRB2) to initiate the RAS/RAF/MAPK kinase 1 (MEK1)/extracellular signal-regulated kinase 1/2 (ERK1/2) signalling cascade. 3) Phoshatidylinositol-3 kinase/protein kinase B (P13K/Akt) pathway: leptin mediates P13K/Akt activation via the insulin receptor substrate 1/2 (IRS1/2). These pathways cause cell proliferation and survival.
