Role of Akt isoforms in IGF-I-mediated signaling and survival in myoblasts.
Oxidative stress has been shown to induce apoptosis in a variety of tissues, while insulin-like growth factor-I (IGF-I) can oppose this effect. We found that H(2)O(2) promoted cell death and apoptosis in C2C12 myoblasts, an effect that was completely prevented by exogenous IGF-I. One downstream mediator of IGF-I survival signaling is the serine/threonine kinase Akt, of which three isoforms have been identified in mammals. We found that Akt1 and Akt3 act on pro-apoptotic target molecules in an isoform-specific manner. Both Akt1 and Akt3 were responsible for phosphorylating FoxO3a at S253 and FoxO1 at T24, while Akt1 alone phosphorylated Bad at S136 and FoxO3a at T32. Our results provide evidence for IGF-I-stimulated isoform-specific actions of Akt on molecules involved in promoting apoptosis.
Matheny
Ronald W
RW
Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Adamo
Martin L
ML
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000201:enzymology / Q000502:physiology*; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494820:Bad protein, mouse; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; D007527:Isoenzymes; D034741:RNA, Small Interfering; D051025:bcl-Associated Death Protein; D007334:Insulin-Like Growth Factor I; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt
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