2000
DOI: 10.1021/bi0015921
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Mechanism of Transmembrane Signaling:  Insulin Binding and the Insulin Receptor

Abstract: Transmembrane signaling via receptor tyrosine kinases generally requires oligomerization of receptor monomers, with the formation of ligand-induced dimers or higher multimers of the extracellular domains of the receptors. Such formations are expected to juxtapose the intracellular kinase domains at the correct distances and orientations for transphosphorylation. For receptors of the insulin receptor family that are constitutively dimeric, or those that form noncovalent dimers without ligands, the mechanism mus… Show more

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Cited by 135 publications
(84 citation statements)
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“…Our results are consistent with studies showing that excessive consumption of alcohol can lead to glucose intolerance [4,5] . These results are contrary to previous in vitro studies showing that regular, moderate alcohol drinkers were more insulinsensitive than abstainers [24] .…”
Section: Discussionsupporting
confidence: 93%
See 1 more Smart Citation
“…Our results are consistent with studies showing that excessive consumption of alcohol can lead to glucose intolerance [4,5] . These results are contrary to previous in vitro studies showing that regular, moderate alcohol drinkers were more insulinsensitive than abstainers [24] .…”
Section: Discussionsupporting
confidence: 93%
“…Long-term exposure to excessive alcohol may lead to glucose intolerance [3,4] . Insulin produces a diverse array of metabolic actions by binding to a heterotetrameric receptor protein consisting of two α and two β subunits [5] . Phosphorylated insulin receptor (IR) binds to and activates IR substrate (IRS), which in turn leads to translocation of glucose transporters to the cell surface via a complicated cascade of signaling events that include phosphatidylinositol 3-kinase (PI3K) and Akt/protein kinase B (PKB) [6,7] .…”
Section: Introductionmentioning
confidence: 99%
“…Signaling by the IR promotes survival (Ottensmeyer et al, 2000;Sciacca et al, 2002), which, when inhibited by HNMPA-(AM 3 ), could trigger apoptosis. Accordingly, HNMPA-(AM 3 )-treated cells were assayed for apoptosis using Annexin V-FITC staining.…”
Section: Resultsmentioning
confidence: 99%
“…The IR is homologous to the IGF-IR, both are members of the receptor tyrosine kinase (RTK) superfamily, and both can be activated by IGF-II (Sciacca et al, 1999). Binding of ligands to the IGF-IR or the IR triggers a signal cascade that leads to a similar activation of downstream effector molecules that regulate cell growth and survival (Ottensmeyer et al, 2000). Our data suggest that latently infected KS cells can grow independent of the IGF-IR, but require IR-dependent signaling for continued growth.…”
Section: Introductionmentioning
confidence: 99%
“…Several models have been proposed for insulin signaling including some in which cross-linking of the two receptor subunits is required for activity (5)(6)(7)(8)(9). For example, it is known that insulin binding to detergent-solubilized IR induces a conformational change that has been correlated with autophosphorylation of the receptor's kinase domain.…”
mentioning
confidence: 99%