The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Open accessAbstract
Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant phosphorylation sites are difficult to identify in cultured cells and to validate in isolated tissues. Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser307, which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1. To monitor phosphorylation of Ser307 in various cell and tissue backgrounds, we prepared a phosphospecific polyclonal antibody designated alphapSer307. This antibody revealed that TNF-alpha, IGF-1, or insulin stimulated phosphorylation of IRS-1 at Ser307 in 3T3-L1 preadipocytes and adipocytes. Insulin injected into mice or rats also stimulated phosphorylation of Ser307 on IRS-1 immunoprecipitated from muscle; moreover, Ser307 was phosphorylated in human muscle during the hyperinsulinemic euglycemic clamp. Experiments in 3T3-L1 preadipocytes and adipocytes revealed that insulin-stimulated phosphorylation of Ser307 was inhibited by LY294002 or wortmannin, whereas TNF-alpha-stimulated phosphorylation was inhibited by PD98059. Thus, distinct kinase pathways might converge at Ser307 to mediate feedback or heterologous inhibition of IRS-1 signaling to counterregulate the insulin response.
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Cites
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Disruption of IRS-2 causes type 2 diabetes in mice
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Self-citationStructure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
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Cited by
Mechanisms for Insulin Resistance: Common Threads and Missing Links
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“Other agents—including insulin in rodent and human tissues—can stimulate phosphorylation of S307 via JNK-independent pathways [39].”
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Self-citationPositive and negative regulation of insulin signaling through IRS-1 phosphorylation
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Metadata
- Authors
- Rui, L., Aguirre, V., Kim, J. K., Shulman, G. I., Lee, A., Corbould, A., Dunaif, A., & White, M. F.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-01-15
- Volume
- 107
- Issue
- 2
- Pages
- 181-189
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2089269477
- Cited by
- 607
- References
- 35
- FWCI
- 12.16
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rui, L., Aguirre, V., Kim, J. K., Shulman, G. I., Lee, A., Corbould, A., Dunaif, A., & White, M. F. (2001). Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. Journal of Clinical Investigation. https://doi.org/10.1172/jci10934
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