Leptin and TGF-beta synergistically regulate VIP cytokine response element transcription.
Leptin was originally described as an adipocyte-derived cytokine that signals to the hypothalamus to regulate food intake and energy expenditure. Leptin signals through the Ob receptor, which is closely related to the gp130 cytokine receptor. Here we show that leptin can induce expression of the neuropeptide gene vasoactive intestinal peptide (VIP) through the VIP cytokine response element, the same element that mediates the response to the gp130 cytokines. Leptin acts synergistically with TGF-beta to activate transcription through this element. Transcriptional responses to leptin are increased when transmitted through ObR mutated at Tyr986, the SHP-2 docking domain, yet this mutation does not alter the synergy between TGF-beta and leptin. These data emphasize the functional similarity between leptin and the gp130 cytokines.
Jones
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Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Symes
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A
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020218:Response Elements / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000187:drug effects / Q000235:genetics*
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D016212:Transforming Growth Factor beta; D014660:Vasoactive Intestinal Peptide