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Review
. 1999 Apr;103(7):931-43.
doi: 10.1172/JCI6609.

Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance

A Virkamäki  1 , K Ueki, C R Kahn
Affiliations
Review

Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance

A Virkamäki et al. J Clin Invest. 1999 Apr.
No abstract available

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Figures

Figure 1
Figure 1
Schematic illustration of major signaling pathways of insulin action. The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins. PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response. PI3-kinase probably modulates the mitogenic response as well.
Figure 2
Figure 2
Protein–protein interaction domains involved in insulin signal transduction. A typical IRS protein contains a PH domain, which targets the protein in plasma membrane, and a PTB domain, which binds to NPXpY motif in the β subunit of the insulin receptor. SH2 domains of SH2 adaptors and SH2 enzymes bind to multiple phosphotyrosines of IRS proteins. SH2 adaptors frequently possess SH3 domains that recognize PXXP motifs of other intracellular proteins, leading to further downstream signal transduction.
Figure 3
Figure 3
Unique spatial compartmentalization of insulin signal transduction. Insulin receptor uses IRS proteins to activate PI3-kinase. Activated insulin receptor binds transiently IRS proteins, which becomes phosphorylated and thereafter bind the regulatory subunits (p85) of PI3-kinase. The IRS-1/PI3-kinase complex translocates to internal membranes, which provide abundant substrates for PI3-kinase and are in close proximity to the GLUT4 vesicle pool, which translocates to the plasma membrane in response to insulin.
See this image and copyright information in PMC

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Publication types