| Modification Notes |
The Insulin receptor substrate (IRS) proteins are key components in signaling from the Insulin receptor. IRS-4 is the most recently characterized member of the IRS family and has an undefined in vivo function. Phosphorylated IRS-4 associates with phosphatidylinositol 3-kinase (PI3-kinase), involved in Insulin-stimulated DNA synthesis, GH-induced tyrosine phosphorylation of IRS-4 and nuclear translocation of Stat5. IRS-4 also associates with IRAS which, when overexpressed, enhances IRS-4-dependent Insulin stimulation of PI3-kinase. The IRS-4 protein exhibits a limited fiber type specific expression in heart and skeletal muscle tissue and has not yet been detected in any mouse or primary human tissue. The absence of IRS-4 in mice causes mild defects in growth, reproduction and glucose homeostasis, while overexpression of IRS-4 increases basal PI3-kinase activity and Akt phosphorylation. Defects in IRS-4-null mice may result from a lower overall blood glucose concentration. |
