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. Author manuscript; available in PMC: 2016 Mar 13.
Published in final edited form as: Circ Res. 2015 Mar 13;116(6):991–1006. doi: 10.1161/CIRCRESAHA.116.305697

Figure 6.

Figure 6

Leptin-melanocortin activation in distinct areas of the brain and through multiple intracellular signaling pathways may differentially regulate appetite, energy expenditure, and arterial pressure. Leptin binding to the leptin receptor (LepR) activates its associated JAK2 tyrosine kinase (Tyr), leading to the autophosphorylation of tyrosine residues on JAK2 and phosphorylation of Tyr985 and Tyr1138. Phosphorylation of Tyr985 activates SHP2/MAPK and phosphorylation of Tyr1183 activates STAT3, a transcription factor. STAT3 activation, in addition to mediating multiple effects of leptin, also induces transcription of SOCS3 which binds to phosphor-Tyr985 and to the LepR-JAK2 complex and has a feedback effect to attenuate LepR-mediated signaling. PTP1B attenuates leptin signaling by dephosphorylation of JAK2. LepR activation of proopiomelanocortin (POMC) neurons causes release α-melanocyte stimulating hormone (α-MSH) which stimulates melanocortin 4 receptors (MC4R) in second-order neurons of the hypothalamus, brainstem, and spinal cord intermediolateral nucleus (IML).