Leptin receptor (OB-R) oligomerizes with itself but not with its closely related cytokine signal transducer gp130.
Leptin (OB) exerts weight-reducing effects in mice. The structure of the receptor for this factor, OB-R, is considerably similar to those of gp130, the common signal transducing receptor component for the interleukin-6 (IL-6) family of cytokines, and leukemia inhibitory factor receptor (LIFR). Since the IL-6 family of cytokines signal through gp130 homodimer or gp130/LIFR heterodimer, we have examined in this study the possible involvement of gp130 and LIFR in leptin signaling through OB-R. Leptin stimulation induces tyrosine phosphorylation of neither gp130 nor LIFR, while LIF stimulation does both. As examined by using two differently epitope-tagged OB-R molecules, the spontaneous homo-oligomerization of OB-R has been elucidated. Ba/F3 cells, which do not express gp130, are non-responsive to leptin and exhibit increased DNA synthesis in response to leptin after transfection of OB-R cDNA alone. OB-R appears to transduce the signal via its homo-oligomerization without interaction with gp130 or LIFR.
Nakashima
K
K
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Narazaki
M
M
Taga
T
T
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D019556:COS Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D000939:Epitopes; D006131:Growth Inhibitors; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011487:Protein Conformation; D011506:Proteins / Q000494:pharmacology; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000378:metabolism*; D054411:Receptors, Leptin; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000939:Epitopes; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; D007377:Interleukin-3; D015850:Interleukin-6; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D004247:DNA