The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
The Direct Involvement of SirT1 in Insulin-induced Insulin Receptor Substrate-2 Tyrosine Phosphorylation
Open accessAbstract
NAD+ -dependent Sir2 family deacetylases and insulin signaling pathway are both conserved across species to regulate aging process. The interplay between these two genetic programs is investigated in this study. Protein deacetylase activity of SirT1, the mammalian homologue of Sir2, was suppressed through either nicotinamide treatment or RNA interference in several cell lines, and these cells displayed impaired insulin responses. Suppression of SirT1 activity also selectively inhibited insulin-induced tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2), whereas it had minimal effect on that of IRS-1. Further analyses showed that both IRS-1 and IRS-2 interacted with SirT1, and the acetylation level of IRS-2 was down-regulated by insulin treatment. Inhibition of SirT1 activity prevented deacetylation and insulin-induced tyrosine phosphorylation of IRS-2. Mutations of four lysine residues to alanine in IRS-2 protein, on the other hand, led to its reduced basal level acetylation and insulin-induced tyrosine phosphorylation. These results suggest a possible regulatory effect of SirT1 on insulin-induced tyrosine phosphorylation of IRS-2, a vital step in insulin signaling pathway, through deacetylation of IRS-2 protein. More importantly, this study may imply a pathway through which Sir2 family protein deacetylases and insulin signaling pathway jointly regulate various metabolic processes, including aging and diabetes.
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Cites
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
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Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
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Suppression of Aging in Mice by the Hormone Klotho
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SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
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The Mammalian SIR2α Protein Has a Role in Embryogenesis and Gametogenesis
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Cited by
The intersection between aging and cardiovascular disease
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SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity
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SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
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Sirtuin signaling in cellular senescence and aging
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Metadata
- Authors
- Zhang, J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 282
- Issue
- 47
- Pages
- 34356-34364
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968157888
- Cited by
- 170
- References
- 9
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
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