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 Sharp; Andrzej Bartke

doi:10.1093/gerona/60.3.293

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 Sharp, Andrzej Bartke

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

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 libitumfed 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 represser 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.

Original language	English (US)
Pages (from-to)	293-300
Number of pages	8
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	60
Issue number	3
DOIs	https://doi.org/10.1093/gerona/60.3.293
State	Published - Mar 2005

ASJC Scopus subject areas

Aging
Geriatrics and Gerontology

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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. / Sharp, Zelton Dave; Bartke, Andrzej.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 60, No. 3, 03.2005, p. 293-300.

Research output: Contribution to journal › Article › peer-review

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title = "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",

abstract = "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 libitumfed 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 represser 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.",

author = "Sharp, {Zelton Dave} and Andrzej Bartke",

note = "Funding Information: ACKNOWLEDGMENTS We acknowledge grant support from the National Institutes of Health (AG19899 to A.B. and AG14674 to Z.D.S). Adriana Nunez-Gavia provided excellent technical expertise. Bandana Chatterjee and Robert Ferry gave helpful suggestions on the manuscript. Sylvia van-Buul-Offers provided especially helpful insights regarding growth hormone, Snell mice, and improvements in the manuscript. Maria Gaczynska and Pawel Osmulski gave valuable help with Western blot protocols. Nahum Sonenberg provided invaluable advice, protocols for the Cap-binding assays, and antibodies for eIF4G1 and eIF4G2. We also wish to acknowledge the helpful suggestions made by the anonymous reviewers.",

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