Open AccessEvidence for Down-Regulation of Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR)-Dependent Translation Regulatory Signaling Pathways in Ames Dwarf Mice
Author(s) -
Z. Dave Sharp,
A. Bartke
Publication year - 2005
Publication title -
the journals of gerontology series a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.134
H-Index - 189
eISSN - 1758-535X
pISSN - 1079-5006
DOI - 10.1093/gerona/60.3.293
Subject(s) - pi3k/akt/mtor pathway , p70 s6 kinase 1 , protein kinase b , biology , eukaryotic initiation factor , signal transduction , mtorc2 , phosphorylation , microbiology and biotechnology , anabolism , kinase , translation (biology) , mtorc1 , endocrinology , messenger rna , biochemistry , gene
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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