Differential Role of Insulin Receptor Substrate (IRS)-1 and IRS-2 in L6 Skeletal Muscle Cells Expressing the Arg1152 → Gln Insulin Receptor
| Informace o vydavateli: | Elsevier BV, 1999. |
|---|---|
| Rok vydání: | 1999 |
| Témata: | medicine.medical_specialty, Glutamine, Arginine, Transfection, environment and public health, Biochemistry, Cell Line, src Homology Domains, Phosphatidylinositol 3-Kinases, Structure-Activity Relationship, chemistry.chemical_compound, Insulin receptor substrate, Internal medicine, medicine, Animals, Phosphorylation, Muscle, Skeletal, Protein kinase A, Molecular Biology, Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, Insulin-like growth factor 1 receptor, biology, Kinase, Intracellular Signaling Peptides and Proteins, Proteins, Tyrosine phosphorylation, Cell Biology, Phosphoproteins, Receptor, Insulin, IRS2, Rats, Cell biology, Insulin receptor, Endocrinology, Amino Acid Substitution, chemistry, Insulin Receptor Substrate Proteins, biology.protein |
| Popis: | In L6 muscle cells expressing the Arg1152 --> Gln insulin receptor (Mut), basal tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was increased by 35% compared with wild-type cells (WT). Upon exposure to insulin, IRS-1 phosphorylation increased by 12-fold in both the Mut and WT cells. IRS-2 was constitutively phosphorylated in Mut cells and not further phosphorylated by insulin. The maximal phosphorylation of IRS-2 in basal Mut cells was paralleled by a 4-fold increased binding of the kinase regulatory loop binding domain of IRS-2 to the Arg1152 --> Gln receptor. Grb2 and phosphatidylinositol 3-kinase association to IRS-1 and IRS-2 reflected the phosphorylation levels of the two IRSs. Mitogen-activated protein kinase activation and [3H]thymidine incorporation closely correlated with IRS-1 phosphorylation in Mut and WT cells, while glycogen synthesis and synthase activity correlated with IRS-2 phosphorylation. The Arg1152 --> Gln mutant did not signal Shc phosphorylation or Shc-Grb2 association in intact L6 cells, while binding Shc in a yeast two-hybrid system and phosphorylating Shc in vitro. Thus, IRS-2 appears to mediate insulin regulation of glucose storage in Mut cells, while insulin-stimulated mitogenesis correlates with the activation of the IRS-1/mitogen-activated protein kinase pathway in these cells. IRS-1 and Shc-mediated mitogenesis may be redundant in muscle cells. |
| Popis souboru: | STAMPA |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.5.3094 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0edbec0f3584f6a8c86576e44147325d https://doi.org/10.1074/jbc.274.5.3094 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....0edbec0f3584f6a8c86576e44147325d |
| Autor: | Renata Auricchio, Emmanuel Van Obberghen, Francesco Oriente, Gerolama Condorelli, Almerinda Cafieri, Claudia Miele, Francesco Beguinot, Matilde Caruso, Dominique Sawka-Verhelle, Véronique Calleja, Pietro Formisano |
| Přispěvatelé: | Miele, C, Caruso, M, Calleja, V, Auricchio, Renata, Oriente, Francesco, Formisano, Pietro, Condorelli, Gerolama, Cafieri, A, Sawka Verhelle, D, Van Obberghen, E, Beguinot, Francesco |
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Glutamine Arginine Transfection environment and public health Biochemistry Cell Line src Homology Domains Phosphatidylinositol 3-Kinases Structure-Activity Relationship chemistry.chemical_compound Insulin receptor substrate Internal medicine medicine Animals Phosphorylation Muscle Skeletal Protein kinase A Molecular Biology Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Insulin-like growth factor 1 receptor biology Kinase Intracellular Signaling Peptides and Proteins Proteins Tyrosine phosphorylation Cell Biology Phosphoproteins Receptor Insulin IRS2 Rats Cell biology Insulin receptor Endocrinology Amino Acid Substitution chemistry Insulin Receptor Substrate Proteins biology.protein |
| Zdroj: | The Journal of biological chemistry 274 (1999): 3094–3102. info:cnr-pdr/source/autori:Miele C, Caruso M, Calleja V, Auricchio R, Oriente F, Formisano P, Condorelli G, Cafieri A, Sawka-Verhelle D, Van Obberghen E, Beguinot F./titolo:Differential role of insulin receptor substrate (IRS)-1 and IRS-2 in L6 skeletal muscle cells expressing the Arg1152--> Gln insulin receptor./doi:/rivista:The Journal of biological chemistry (Print)/anno:1999/pagina_da:3094/pagina_a:3102/intervallo_pagine:3094–3102/volume:274 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.5.3094 |
| Popis: | In L6 muscle cells expressing the Arg1152 --> Gln insulin receptor (Mut), basal tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was increased by 35% compared with wild-type cells (WT). Upon exposure to insulin, IRS-1 phosphorylation increased by 12-fold in both the Mut and WT cells. IRS-2 was constitutively phosphorylated in Mut cells and not further phosphorylated by insulin. The maximal phosphorylation of IRS-2 in basal Mut cells was paralleled by a 4-fold increased binding of the kinase regulatory loop binding domain of IRS-2 to the Arg1152 --> Gln receptor. Grb2 and phosphatidylinositol 3-kinase association to IRS-1 and IRS-2 reflected the phosphorylation levels of the two IRSs. Mitogen-activated protein kinase activation and [3H]thymidine incorporation closely correlated with IRS-1 phosphorylation in Mut and WT cells, while glycogen synthesis and synthase activity correlated with IRS-2 phosphorylation. The Arg1152 --> Gln mutant did not signal Shc phosphorylation or Shc-Grb2 association in intact L6 cells, while binding Shc in a yeast two-hybrid system and phosphorylating Shc in vitro. Thus, IRS-2 appears to mediate insulin regulation of glucose storage in Mut cells, while insulin-stimulated mitogenesis correlates with the activation of the IRS-1/mitogen-activated protein kinase pathway in these cells. IRS-1 and Shc-mediated mitogenesis may be redundant in muscle cells. |
| Databáze: | OpenAIRE |
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