These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Tumor necrosis factor promotes phosphorylation and binding of insulin receptor substrate 1 to phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.
    Author: Guo D, Donner DB.
    Journal: J Biol Chem; 1996 Jan 12; 271(2):615-8. PubMed ID: 8557661.
    Abstract:
    Chronic incubation of 3T3-L1 adipocytes with tumor necrosis factor (TNF) induces a state of insulin resistance characterized by a diminished ability of insulin to induce phosphorylation of the beta subunit of its own receptor and insulin receptor substrate 1 (IRS-1). When adipocytes are briefly pretreated with TNF and then stimulated with insulin, tyrosine phosphorylation of IRS-1 increases above the level induced by insulin alone. By itself, TNF induces the time-dependent tyrosine phosphorylation of proteins in 3T3-L1 adipocytes. Among these is IRS-1, a docking protein with tyrosine phosphorylation sites that bind cytoplasmic signaling molecules that contain Src homology 2 (SH2) domains. TNF stimulation of 3T3-L1 adipocytes also promotes the association of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with IRS-1 and also its tyrosine phosphorylation. In murine 3T3-L1 adipocytes, IRS-1 and PI 3-kinase phosphorylation and the association of these proteins are promoted by murine TNF, which interacts with the type 1 and type 2 TNF receptors. Human TNF, which binds to the murine type 1 TNF receptor selectively, also promotes IRS-1 phosphorylation and binding of IRS-1 to PI 3-kinase. This is the first demonstration that a member of the TNF/nerve growth factor receptor superfamily can use an IRS-1 signaling system as a component of its cellular response and provides a mechanism through which TNF receptors may engage downstream elements in signaling pathways.
    [Abstract] [Full Text] [Related] [New Search]