Regulation of insulin-stimulated tyrosine phosphorylation of Shc and Shc/Grb2 association in liver, muscle, and adipose tissue of epinephrine- and streptozotocin-treated rats.
Shc protein phosphorylation has been extensively characterized as the initial step that activates a complex mitogenic pathway through its association with Grb2. In the present study, we investigated the adrenergic control of insulin-induced Shc phosphorylation and Shc-Grb2 association, and the modulating effect of streptozotocin-induced diabetes mellitus on Shc phosphorylation and Shc/Grb2 association. Acute treatment with epinephrine, which leads to a normoglycemic insulin-resistant state, does not affect insulin-induced Shc tyrosine phosphorylation or Shc-Grb2 association in liver, muscle, or fat. By contrast, a significant increase in insulin-induced Shc phosphorylation is observed in liver and muscle of rats treated with streptozotocin. The association of Shc/Grb2 is also increased in both tissues following insulin treatment. These data suggest that while epinephrine preserves the insulin-induced phosphorylation of Shc and the mitogenic pathway stimulated by Shc-Grb2 association, treatment with streptozotocin leads to a tissue-specific increase in the activity of the initial step that ultimately results in the activation of the Shc/Grb2 mitogenic pathway.
Páez-Espinosa
V
V
Departamento de Fisiologia e Biofísica, Instituto de Biologia, Faculdade de Ciencias Médicas, Universidade Estadual de Campinas, SP, Brazil.
Rocha
E M
EM
Velloso
L A
LA
Saad
M J
MJ
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000273:Adipose Tissue / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D051380:GRB2 Adaptor Protein; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000322:Adrenergic Agonists; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D007328:Insulin; D011506:Proteins; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D011972:Receptor, Insulin; D004837:Epinephrine