The ins and outs of leptin receptor activation.
The adipocyte-derived hormone leptin signals the status of body energy stores by activating its receptor in hypothalamic nuclei. In contrast to the initial expectations, leptin treatment of human obesity was largely unsuccessful. One explanation for this is the marked leptin resistance, which likely operates in part at the receptor level. The leptin receptor is a member of the class I cytokine receptor family, which uses the Janus kinase/signal transducer and activator of transcription pathway as a major signaling route. In this review, we focus on the molecular mechanisms underlying leptin receptor activation. Different modes of leptin-induced clustering of the ectodomains and the subsequent signaling events will be discussed.
Zabeau
Lennart
L
The Flanders Interuniversity Institute for Biotechnology, Department of Medical Protein Research (VIB9), Ghent University, Faculty of Medicine and Health Sciences, Baertsoenkaai 3, B-9000 Ghent, Belgium.
Lavens
Delphine
D
Peelman
Frank
F
Eyckerman
Sven
S
Vandekerckhove
Joël
J
Tavernier
Jan
J
D000818:Animals; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D054411:Receptors, Leptin; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D015534:Trans-Activators; C515448:LEPR protein, human