Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / chemistry
-
Antigens, CD / metabolism*
-
B-Lymphocytes / drug effects
-
B-Lymphocytes / metabolism
-
Blotting, Western
-
COS Cells / metabolism
-
Carrier Proteins / chemistry*
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism*
-
Cytokine Receptor gp130
-
DNA / biosynthesis
-
DNA / drug effects
-
DNA-Binding Proteins / metabolism
-
Epitopes
-
Growth Inhibitors*
-
Interleukin-3 / pharmacology
-
Interleukin-6*
-
Leptin
-
Leukemia Inhibitory Factor
-
Leukemia Inhibitory Factor Receptor alpha Subunit
-
Lymphokines*
-
Membrane Glycoproteins / chemistry
-
Membrane Glycoproteins / metabolism*
-
Mice
-
Phosphorylation
-
Precipitin Tests
-
Protein Conformation
-
Proteins / pharmacology
-
Receptors, Cell Surface*
-
Receptors, Cytokine / metabolism*
-
Receptors, Leptin
-
Receptors, OSM-LIF
-
Recombinant Proteins / genetics
-
Recombinant Proteins / immunology
-
Recombinant Proteins / metabolism
-
STAT3 Transcription Factor
-
Signal Transduction
-
Trans-Activators / metabolism
-
Transfection
-
Tyrosine / metabolism
Substances
-
Antigens, CD
-
Carrier Proteins
-
DNA-Binding Proteins
-
Epitopes
-
Growth Inhibitors
-
Il6st protein, mouse
-
Interleukin-3
-
Interleukin-6
-
Leptin
-
Leukemia Inhibitory Factor
-
Leukemia Inhibitory Factor Receptor alpha Subunit
-
Lif protein, mouse
-
Lifr protein, mouse
-
Lymphokines
-
Membrane Glycoproteins
-
Proteins
-
Receptors, Cell Surface
-
Receptors, Cytokine
-
Receptors, Leptin
-
Receptors, OSM-LIF
-
Recombinant Proteins
-
STAT3 Transcription Factor
-
Stat3 protein, mouse
-
Trans-Activators
-
leptin receptor, mouse
-
Cytokine Receptor gp130
-
Tyrosine
-
DNA