Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1996 Jan 12;271(2):615-8.

Tumor necrosis factor promotes phosphorylation and binding of insulin receptor substrate 1 to phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.

Author information

1
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.

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.

PMID:
8557661
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center