TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver

作者: K. Du

DOI: 10.1126/SCIENCE.1079817

关键词:

摘要: Insulin resistance is a major hallmark in the development of type II diabetes, which characterized by failure insulin to promote glucose uptake muscle and suppress production liver. The serine-threonine kinase Akt (PKB) principal target signaling that inhibits hepatic output when available from food. Here we show TRB3, mammalian homolog Drosophila tribbles, functions as negative modulator Akt. TRB3 expression induced liver under fasting conditions, disrupts binding directly blocking activation kinase. Amounts RNA protein were increased livers db/db diabetic mice compared with those wild-type mice. Hepatic overexpression amounts comparable promoted hyperglycemia intolerance. Our results suggest that, interfering activation, contributes individuals susceptibility diabetes.

参考文章(22)
Stéphanie A. Backman, Vuk Stambolic, Akira Suzuki, Jillian Haight, Andrew Elia, James Pretorius, Ming-Sound Tsao, Patrick Shannon, Brad Bolon, Gwen O. Ivy, Tak W. Mak, Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nature Genetics. ,vol. 29, pp. 396- 403 ,(2001) , 10.1038/NG782
Mary C. Gannon, Frank Q. Nuttall, Effect of prolonged starvation on glycogen synthase and glycogen synthase phosphatase activity in rat heart. Journal of Nutrition. ,vol. 114, pp. 2147- 2154 ,(1984) , 10.1093/JN/114.11.2147
Sauveur-Michel Maira, Ivana Galetic, Derek P Brazil, Stefanie Kaech, Evan Ingley, Marcus Thelen, Brian A Hemmings, Carboxyl-Terminal Modulator Protein (CTMP), a Negative Regulator of PKB/Akt and v-Akt at the Plasma Membrane Science. ,vol. 294, pp. 374- 380 ,(2001) , 10.1126/SCIENCE.1062030
Yasuhiro Mitsuuchi, Steven W. Johnson, Steven Moonblatt, Joseph R. Testa, Translocation and activation of AKT2 in response to stimulation by insulin Journal of Cellular Biochemistry. ,vol. 70, pp. 433- 441 ,(1998) , 10.1002/(SICI)1097-4644(19980915)70:4<433::AID-JCB1>3.0.CO;2-K
Derek P. Brazil, Brian A. Hemmings, Ten years of protein kinase B signalling: a hard Akt to follow. Trends in Biochemical Sciences. ,vol. 26, pp. 657- 664 ,(2001) , 10.1016/S0968-0004(01)01958-2
Juan Mata, Silvia Curado, Anne Ephrussi, Pernille Rørth, Tribbles Coordinates Mitosis and Morphogenesis in Drosophila by Regulating String/CDC25 Proteolysis Cell. ,vol. 101, pp. 511- 522 ,(2000) , 10.1016/S0092-8674(00)80861-2
Matthew J. Brady, Francis J. Bourbonais, Alan R. Saltiel, The Activation of Glycogen Synthase by Insulin Switches from Kinase Inhibition to Phosphatase Activation during Adipogenesis in 3T3-L1 Cells Journal of Biological Chemistry. ,vol. 273, pp. 14063- 14066 ,(1998) , 10.1074/JBC.273.23.14063
Han Cho, James Mu, Jason K Kim, Joanne L Thorvaldsen, Qingwei Chu, E Bryan Crenshaw III, Klaus H Kaestner, Marisa S Bartolomei, Gerald I Shulman, Morris J Birnbaum, Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ) Science. ,vol. 292, pp. 1728- 1731 ,(2001) , 10.1126/SCIENCE.292.5522.1728