Regulation of cardiac Jak-2 in animal models of insulin resistance.
Insulin induces phosphorylation and activation of JAK2 tyrosine, as well as its association with STAT1 and SHP2 in insulin-sensitive tissues of intact rats, thus demonstrating a new pathway in transduction of insulin signals. We investigated this pathway in hearts of rats in three situations of insulin resistance: 72 h of fasting, chronic treatment with dexamethasone, and acute treatment with epinephrine. The acute treatment with epinephrine showed no difference in insulin-induced JAK2 tyrosine phosphorylation or JAK2/STAT1 and JAK2/SHP2 association in comparison with the control. In fasted rats the JAK2 protein concentration decreased, accompanied by a decrease in the stoichiometry of the phosphorylation to 70%, an increase in association of JAK2/STAT1 to 160%, and a decrease in JAK2/SHP2 association to 85%. In the dexamethasone-treated group, the JAK2 protein concentrations increased but the stoichiometry of its phosphorylation decreased to 20%, whereas the JAK2/STAT1 and JAK2/SHP2 associations changed by 70% and 170%, respectively. In fasting and dexamethasone-treated rats, therefore, insulin-induced JAK2 tyrosine phosphorylation decreases, and the JAK2 protein expression is differentially regulated such that the insulin-induced JAK2 association with SHP2 and STAT1 shows opposite interactions with the kinase.
Rojas
F A
FA
Departamento de Clínica Médica, FCM, UNICAMP, Campinas, SP, Brasil.
Carvalho
C R
CR
Paez-Espinosa
V
V
Saad
M J
MJ
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005215:Fasting; D007333:Insulin Resistance / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D015534:Trans-Activators; D014443:Tyrosine; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat; D004837:Epinephrine