Abstract
We report herein the characterization of activities of signal transduction for three types of leptin receptors (OBRs) from rats, the OBRa, OBRb, and OBRb with fa mutation (OBRb-fa), by measurement of the levels of tyrosine phosphorylation of STAT3 (signal transducers and activators of transcription 3) and MAPK (mitogen-activated protein kinase), which are induced by leptin stimulation of CHO cells stably expressing the OBR (CHO-OBRb, CHO-OBRa, or CHO-OBRb-fa cells). As the result of leptin stimulation, enhanced levels of tyrosine phosphorylation of STAT3 and MAPK were detected in CHO-OBRb cells. In CHO-OBRb-fa cells, enhancement levels for both were lower than those in CHO-OBRb cells. In CHO-OBRa cells, only the phosphorylation of MAPK was detected. These data suggest that these reduced signaling activities cause obesity in fa/fa rats and that OBRa, which has been generally thought to be inactive at signaling, actually transmits signals through the MAPK pathway.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / classification
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cricetinae
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Gene Expression Regulation
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Leptin
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases*
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Mutation
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Phosphorylation
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Proteins / metabolism*
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Rats
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Receptors, Cell Surface*
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Receptors, Cytokine / classification
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism*
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Receptors, Leptin
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Recombinant Proteins / metabolism
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STAT3 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism
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Transcription, Genetic
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Leptin
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Proteins
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Receptors, Cell Surface
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Receptors, Cytokine
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Receptors, Leptin
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Recombinant Proteins
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STAT3 Transcription Factor
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Stat3 protein, rat
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Trans-Activators
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases