Leptin Triggers a Signaling Cascade That Regulates Gene Expression

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The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAK-STAT system (Fig. 23-34; see Fig. 12-9). The lep-tin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The @-Tyr residues become docking sites for three proteins that are signal transducers and activators of transcription (STATs 3, 5, and 6, sometimes called fat-STATS). The docked STATs are then phosphorylated on Tyr residues by the

Leptin receptor monomer

Plasma membrane

Leptin receptor monomer

Plasma membrane

Plasma Membrane Leptin Receptor Monomer

Cytosol

Nucleus

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