Functional STAT 1 and 3 signaling by the leptin receptor (OB-R); reduced expression of the rat fatty leptin receptor in transfected cells.
The leptin receptor (OB-R) bears homology to members of the class I cytokine receptor family. We demonstrate that leptin binding to OB-R stimulates formation of STAT-1 and STAT-3 complexes, thereby defining transcriptional motifs for genes that are under leptin control. Transfected fa OB-R bound leptin with equal affinity to that of wild type OB-R. fa OB-R abundance was about 7 fold reduced compared to control cells. Surprisingly, the low level of fa OB-R is fully capable of activating the STAT signal transduction pathway. We discuss plausible explanations for the obese phenotype in Zucker fatty rats.
Rosenblum
C I
CI
Department of Genetics & Molecular Biology, Merck Research Laboratories, Merck & Co., Rahway, NJ 07065, USA.
Tota
M
M
Cully
D
D
Smith
T
T
Collum
R
R
Qureshi
S
S
Hess
J F
JF
Phillips
M S
MS
Hey
P J
PJ
Vongs
A
A
Fong
T M
TM
Xu
L
L
Chen
H Y
HY
Smith
R G
RG
Schindler
C
C
Van der Ploeg
L H
LH
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000502:physiology*; D002460:Cell Line; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007700:Kinetics; D020738:Leptin; D051379:Mice; D009765:Obesity; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000096:biosynthesis; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
D002352:Carrier Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D020738:Leptin; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494081:Stat1 protein, rat; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; C515447:leptin receptor, mouse