Matches in SemOpenAlex for { <https://semopenalex.org/work/W2005115428> ?p ?o ?g. }
Showing items 1 to 40 of
40
with 100 items per page.
- W2005115428 endingPage "tw424" @default.
- W2005115428 startingPage "tw424" @default.
- W2005115428 abstract "Hafner et al . used an RNA aptamer displacement assay to identify new small molecule inhibitors of the guanine nucleotide exchange factor (GEF) family called cytohesins, which stimulate the activity of the ADP ribosylation factors (ARFs). The most potent and selective of these molecules was named SecinH3. Fuss et al . found that mutations in the Drosophila homolog of cytohesin, a protein called Steppke, caused a phenotype very similar to that seen with insulin signaling defects--small overall fly size at each stage of development but no impairment in eating. Feeding of SecinH3 to flies caused the same phenotype. Both the steppke-mutant flies and the SecinH3-treated flies exhibited biochemical and transcriptional evidence of loss of insulin signaling. Cytohesin appeared to act upstream of activation of phosphoinositide 3-kinase (PI3K), because the steppke-mutant phenotype was alleviated by expression of a constitutively active form of PI3K. Hafner et al . showed that SecinH3 inhibited insulin-dependent signaling in cultured HepG2 cells, a human liver cell line. Insulin also stimulated GTP loading of ARF6, which was blocked by SecinH3. Insulin signaling was blocked at the step of phosphorylation of insulin receptor substrate 1 (IRS1), but insulin receptor phosphorylation was not affected. Coimmunoprecipitation experiments showed that SecinH3 decreased the formation of an insulin-induced complex of cytohesin 2, cytohesin 3, ARF6, the insulin receptor, and IRS1. Mice fed SecinH3 exhibited signs of hepatic insulin resistance and increased circulating insulin, phenomena that are thought to cause type 2 diabetes in humans. Thus, alterations in cytohesin function may contribute to metabolic disorders (see Jackson for discussion). M. Hafner, A. Schmitz, I. Grune, S. G. Srivatsan, B. Paul, W. Kolanus, T. Quast, E. Kremmer, I. Bauer, M. Famulok, Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature 444 , 941-944 (2006). [PubMed] B. Fuss, T. Becker, I. Zinke, M. Hoch, The cytohesin Steppke is essential for insulin signalling in Drosophila . Nature 444 , 945-948 (2006). [PubMed] C. Jackson, Kicking off the insulin cascade. Nature 444 , 833-834 (2006). [PubMed]" @default.
- W2005115428 created "2016-06-24" @default.
- W2005115428 creator A5056409786 @default.
- W2005115428 date "2006-12-12" @default.
- W2005115428 modified "2023-09-26" @default.
- W2005115428 title "Cytohesins Crucial for Hepatic Response to Insulin" @default.
- W2005115428 doi "https://doi.org/10.1126/stke.3662006tw424" @default.
- W2005115428 hasPublicationYear "2006" @default.
- W2005115428 type Work @default.
- W2005115428 sameAs 2005115428 @default.
- W2005115428 citedByCount "0" @default.
- W2005115428 crossrefType "journal-article" @default.
- W2005115428 hasAuthorship W2005115428A5056409786 @default.
- W2005115428 hasConcept C126322002 @default.
- W2005115428 hasConcept C2779306644 @default.
- W2005115428 hasConcept C71924100 @default.
- W2005115428 hasConceptScore W2005115428C126322002 @default.
- W2005115428 hasConceptScore W2005115428C2779306644 @default.
- W2005115428 hasConceptScore W2005115428C71924100 @default.
- W2005115428 hasIssue "366" @default.
- W2005115428 hasLocation W20051154281 @default.
- W2005115428 hasOpenAccess W2005115428 @default.
- W2005115428 hasPrimaryLocation W20051154281 @default.
- W2005115428 hasRelatedWork W1983641721 @default.
- W2005115428 hasRelatedWork W1984553087 @default.
- W2005115428 hasRelatedWork W2023856112 @default.
- W2005115428 hasRelatedWork W2026226896 @default.
- W2005115428 hasRelatedWork W2030111077 @default.
- W2005115428 hasRelatedWork W2058829258 @default.
- W2005115428 hasRelatedWork W2066345847 @default.
- W2005115428 hasRelatedWork W2124070488 @default.
- W2005115428 hasRelatedWork W2125235918 @default.
- W2005115428 hasRelatedWork W2130904138 @default.
- W2005115428 hasVolume "2006" @default.
- W2005115428 isParatext "false" @default.
- W2005115428 isRetracted "false" @default.
- W2005115428 magId "2005115428" @default.
- W2005115428 workType "article" @default.