The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors.
The leptin receptor (OB-R) is a single membrane-spanning protein that mediates the weight regulatory effects of leptin (OB protein). The mutant allele (db) of the OB-R gene encodes a protein with a truncated cytoplasmic domain that is predicted to be functionally inactive. Several mRNA splice variants encoding OB-Rs with different length cytoplasmic domains have been detected in various tissues. Here we demonstrate that the full-length OB-R (predominantly expressed in the hypothalamus), but not a major naturally occurring truncated form or a mutant from found in db/db mice, can mediate activation of signal transducer and activator of transcription (STAT) proteins and stimulate transcription through interleukin 6 responsive gene elements. Reconstitution experiments suggest that, although OB-R mediates intracellular signals with a specificity similar to interleukin 6-type cytokine receptors, signaling appears to be independent of the gp130 signal transducing component of the interleukin 6-type cytokine receptors.
Baumann
H
H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm, Buffalo, NY 14263, USA.
Morella
K K
KK
White
D W
DW
Dembski
M
M
Bailon
P S
PS
Kim
H
H
Lai
C F
CF
Tartaglia
L A
LA
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D051379:Mice; D008894:Milk Proteins; D009765:Obesity / Q000503:physiopathology; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D015703:Antigens, CD; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D008894:Milk Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse