Leptin promotes the tyrosine phosphorylation of SHC proteins and SHC association with GRB2. 2002

O Gualillo, and S Eiras, and D W White, and C Diéguez, and F F Casanueva
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

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.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071425 Src Homology 2 Domain-Containing, Transforming Protein 1 An SHC-signaling adaptor protein that transduces PHOSPHOTYROSINE-dependent signals downstream of RECEPTOR PROTEIN-TYROSINE KINASES and non-receptor tyrosine kinases. It is required for TGF-BETA-induced CELL MIGRATION; NEOLPASM INVASION; and METASTASIS of BREAST NEOPLASMS; its SH2 DOMAIN is essential for tumor survival. It also functions in signaling downstream of ANGIOPOIETIN RECEPTOR TIE-2, regulating the migration of ENDOTHELIAL CELLS; and PHYSIOLOGIC NEOVASCULARIZATION. SHC (Src Homology 2 Domain-Containing) Transforming Protein 1,SHC-Transforming Protein 1,SHC1 (Src Homology 2 Domain-Containing) Protein,SHC1 Protein,ShcA Protein,Src Homology 2 Domain-Containing-Transforming Protein C1,SHC Transforming Protein 1,Src Homology 2 Domain Containing Transforming Protein C1,Src Homology 2 Domain Containing, Transforming Protein 1
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections

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