Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:293-300 (2005)
© 2005 The Gerontological Society of America

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

Zelton Dave Sharp1, and Andrzej Bartke2

1 Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio.
2 Department of Physiology, Southern Illinois University School of Medicine, Carbondale.

Address correspondence to Zelton D. Sharp, Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245. E-mail: sharp{at}uthscsa.edu

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.






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