Identification and expression cloning of a leptin receptor, OB-R.
The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus. A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.
Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139, USA.
L A
LA
Tartaglia
M
M
Dembski
X
X
Weng
N
N
Deng
J
J
Culpepper
R
R
Devos
G J
GJ
Richards
L A
LA
Campfield
F T
FT
Clark
J
J
Deeds
C
C
Muir
S
S
Sanker
A
A
Moriarty
K J
KJ
Moore
J S
JS
Smutko
G G
GG
Mays
E A
EA
Wool
C A
CA
Monroe
R I
RI
Tepper
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002831:Choroid Plexus / Q000502:physiology / Q000648:ultrastructure; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000302:isolation & purification; D054411:Receptors, Leptin
C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse