Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in the murine leptin receptor.
The leptin system provides a link between adipose mass and the central nervous system. The appetite suppressing effects of leptin are impaired in most obese patients and some mutant mice strains. Herein we describe how suppressor of cytokine signalling 3 (SOCS3), a potential mediator of this leptin resistance is recruited into the activated murine leptin receptor complex. Using a functional assay based on inhibition of leptin mediated reporter induction, and using phosphopeptide affinity chromatography we show binding of SOCS3 to the highly conserved phosphorylated Tyr-985 and Tyr-1077 motifs within the mouse leptin receptor.
Eyckerman
S
S
Flanders' Interuniversity Institute for Biotechnology, Department of Medical Protein Research, Ghent University, Faculty of Medicine and Health Sciences, Ghent, Belgium.
Broekaert
D
D
Verhee
A
A
Vandekerckhove
J
J
Tavernier
J
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002846:Chromatography, Affinity; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016716:PC12 Cells; D010748:Phosphopeptides / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; D016415:Sequence Alignment; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014162:Transfection; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C515448:LEPR protein, human; D010748:Phosphopeptides; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; C106644:SOCS3 protein, human; C491411:Socs3 protein, mouse; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C515447:leptin receptor, mouse; D014443:Tyrosine