The insulin receptor substrate 2 (IRS-2) protein is one of the major insulinsignaling substrates. In the present study, we investigated the role of IRS-2 in skin epidermal keratinocytes and dermal fibroblasts. Even though skin is not a classical insulin target tissue, we have previously demonstrated that insulin, via the insulin receptor (IR), is essential for normal skin cell physiology. To id...

Insulin receptor substrate-1 (IRS-1) is an adaptor protein for insulin-like growth factor (IGF) signaling and it is presumed associated with cancer development, progression or clinical outcome of patients harboring solid tumors. Therefore, we investigated by immunohistochemistry, the expression of IRS-1 in the tumor tissues from 94 patients who were diagnosed as stage I non-small cell lung canc...

Insulin receptor substrate-1 (IRS-1) is a multi-domain protein that mediates signal transduction from receptors for insulin and other growth factors to a variety of downstream molecules through both tyrosine-phosphorylation-dependent and -independent interactions. While the tyrosine-phosphorylation-dependent interactions mediated by IRS-1 have been well characterized, the molecular basis underl...

The insulin receptor substrate 2 (IRS-2) protein is one of the major insulin-signaling substrates. In the present study, we investigated the role of IRS-2 in skin epidermal keratinocytes and dermal fibroblasts. Although skin is not a classical insulin target tissue, we have previously demonstrated that insulin, via the insulin receptor, is essential for normal skin cell physiology. To identify ...

OBJECTIVE Angiotensin II has been implicated in the pathogenesis of the vascular complications of insulin resistance. Recently, serine phosphorylation and degradation of insulin receptor substrate-1 (IRS-1) were shown to inhibit Akt activation and reduce glucose uptake. Therefore, we examined the effects of chronic angiotensin II treatment on IRS-1 phosphorylation and protein expression in vasc...

Organ weight was compared in adult mice with deletion of one (IRS-1) or both (IRS-1) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1 littermates. IRS-1 mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1 mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body w...

The insulin receptor substrate 1 (IRS-1) can translocate to the nuclei and nucleoli of several types of cells. Nuclear translocation can be induced by an activated insulin-like growth factor 1 receptor (IGF-IR), and by certain oncogenes, such as the Simian virus 40 T antigen and v-src. We have asked whether IRS-2 could also translocate to the nuclei. In addition, we have studied the effects of ...

Insulin receptor substrates (IRS-1 and -2) are essential for intracellular signaling by insulin and IGF-I, anabolic regulators of bone metabolism. Mice lacking the IRS-1 gene IRS-1(-/-) showed severe osteopenia with low bone turnover. IRS-1 was expressed in osteoblasts, but not in osteoclasts, of wild-type (WT) mice. IRS-1(-/-) osteoblasts treated with insulin or IGF-I failed to induce tyrosine...

Vascular endothelial growth factor (VEGF) isoforms exert their biological effects through receptors that possess intrinsic tyrosine kinase activity. Whether VEGF binding to its receptors recruits insulin receptor substrate (IRS) family of docking proteins to the receptor is not known. Following incubation of mouse kidney proximal tubular epithelial cells with VEGF, we observed an increase in ty...

OBJECTIVE Insulin resistance in skeletal muscle plays a critical role in the pathogenesis of type 2 diabetes, yet the cellular mechanisms responsible for insulin resistance are poorly understood. In this study, we examine the role of serine phosphorylation of insulin receptor substrate (IRS)-1 in mediating fat-induced insulin resistance in skeletal muscle in vivo. RESEARCH DESIGN AND METHODS ...