Leptin promotes the tyrosine phosphorylation of SHC proteins and SHC association with GRB2.
The identification and characterization of proteins that become tyrosine phosphorylated in response to growth factor stimulation is critical for furthering our understanding of the signal transduction pathways involved in the regulation of cell proliferation, differentiation as well as metabolic activities. In this report, we demonstrate for the first time, that leptin is able to induce the tyrosine phosphorylation of the SH(2) containing protein SHC. These studies have been carried out on a human embryonic cell line (HEK 293) transfected with the cDNA encoding for the long form of the leptin receptor and stably expressing the receptor itself. We also shown that upon tyrosine phosphorylation, SHC associated with the adaptor protein, Grb(2). The formation of this complex may directly link tyrosine phosphorylation events to Ras activation and may be a critical step in proliferation and/or differentiation of cells. In conclusion, these results indicate that leptin receptor, after binding the ligand, activates several pathways for signal transduction that might lead to mitogenic effect.
Gualillo
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O
Complexo Hospitalario Universitario de Santiago (CHUS), Research AREA: Research Laboratory No. 4, Planta Baja Zona Metabolopatias, Trav. Choupana sn, 15706 Santiago de Compostela, Spain. gualillo@usc.es
Eiras
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S
White
D W
DW
Diéguez
C
C
Casanueva
F F
FF
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D051380:GRB2 Adaptor Protein; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C515448:LEPR protein, human; D020738:Leptin; D046911:Macromolecular Substances; D020033:Protein Isoforms; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases