title: Insulin-induced tyrosine phosphorylation of Shc in liver, muscle and adipose tissue of insulin resistant rats.
abstract: Insulin stimulates rapid tyrosine phosphorylation of the protein Shc, which subsequently binds to Grb2, resulting in the activation of a complex mitogenic signaling network. In this study, we examined the levels of Shc protein, its phosphorylation state and Shc-Grb2 association in liver, muscle and adipose tissue before and after insulin administration in three animal models of insulin resistance (chronic dexamethasone treatment, 72-h starvation and aging). There were no differences in Shc protein expression between tissues from control and insulin resistant animals. In fasted hypoinsulinemic rats, there was a decrease in insulin-induced Shc phosphorylation in liver and adipose tissue. However, a significant increase in Shc phosphorylation was observed in liver and muscle from dexamethasone-treated hyperinsulinemic rats and in liver, muscle and adipose tissue of hyperinsulinemic 20-month-old rats. Alterations in Shc phosphorylation correlated well with the level of Shc-Grb2 association. These results indicate that Shc tyrosyl phosphorylation and Shc-Grb2 association are regulated in the different types of insulin resistance and that this regulation is apparently related to the animals' plasma insulin levels. The Shc-Grb2 association is directly related to the insulin-induced tyrosyl phosphorylation of Shc.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, SP, Brazil.
authors.forename: E V
authors.initials: EV
authors.lastname: Páez-Espinosa
authors.forename: E M
authors.initials: EM
authors.lastname: Rocha
authors.forename: L A
authors.initials: LA
authors.lastname: Velloso
authors.forename: A C
authors.initials: AC
authors.lastname: Boschero
authors.forename: M J
authors.initials: MJ
authors.lastname: Saad
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004435:Eating; D066246:ErbB Receptors / Q000378:metabolism; D005215:Fasting; D051380:GRB2 Adaptor Protein; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001786:Blood Glucose; 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; D003907:Dexamethasone; D066246:ErbB Receptors; D006854:Hydrocortisone