Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice.
How growth hormone (GH) stimulates protein synthesis is unknown. Phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways balance anabolic and catabolic activities in response to nutrients and growth factor signaling. As a test of GH signaling, immunoassays of two downstream translation regulatory proteins were compared in ad libitum-fed 2-month-old normal and Ames (Prop1df) dwarf mice. Phosphorylation of the p70 and p85 isoforms of S6 kinase 1 in liver and the p70 isoform in gastrocnemius muscle were significantly decreased in dwarfs. Messenger RNA (mRNA) Cap-binding demonstrated significantly higher levels of translation repressor 4E-BP1/eukaryotic initiation factor 4E (eIF4E) (coprecipitates) from dwarf livers, but not muscle. Consistent with these binding data, significantly less phosphorylation of 4E-BP1 was documented in dwarf liver. These data suggest a link between GH signaling and translation control in a model of extended longevity.
Sharp
Zelton Dave
ZD
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, Texas 78245, USA. sharp@uthscsa.edu
Bartke
Andrzej
A
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D004392:Dwarfism / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D013006:Growth Hormone / Q000378:metabolism*; D015151:Immunoblotting; D008099:Liver / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000201:enzymology; D010766:Phosphorylation; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D046509:Tissue Culture Techniques
D005819:Genetic Markers; D013006:Growth Hormone; D019870:1-Phosphatidylinositol 4-Kinase; D020123:Sirolimus