Leptin receptor signal transduction: OBRa and OBRb of fa type.
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.
Yamashita
T
T
Department of Laboratory Medicine, University of Tokushima, Japan.
Murakami
T
T
Otani
S
S
Kuwajima
M
M
Shima
K
K
D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D020738:Leptin; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases