IRS-1 is an insulin receptor substrate that undergoes tyrosine phosphorylation and associates with the phosphatidylinositol (PtdIns) 3'-kinase immediately after insulin stimulation. Recombinant IRS-1 protein was tyrosine phosphorylated by the insulin receptor in vitro and associated with the PtdIns 3'-kinase from lysates of quiescent 3T3 fibroblasts. Bacterial fusion proteins containing the src...

Insulin receptor substrate-2 (IRS-2) is a multisite docking protein implicated in mitogenic signaling after activation of the insulin and insulin-like growth factor (IGF)-I receptors. In the present study, we characterized IRS-2 expression and function in human pancreatic cancer. IRS-2 mRNA and protein were expressed in ASPC-1 and COLO-357 human pancreatic cancer cell lines. Insulin, IGF-I, and...

In addition to a role in response to insulin and insulin-like growth factors, insulin receptor substrate 1 (IRS-1) is phosphorylated in response to IL-4, the interferons (IFNs) and oncostatin M (OSM). Here mutant cell lines lacking JAK1, JAK2, or Tyk2 were used to determine the role(s) of the Janus kinase (JAK) family of protein-tyrosine kinases in IRS-1 phophorylation. 32D cells, which do not ...

Insulin resistance is associated with cardiovascular disease. Impaired insulin receptor substrate (IRS)–mediated signal transduction is a major contributor to insulin resistance. Recently, IRS-1 phosphorylation at serine 307 by stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) has been highlighted as a molecular event that causes insulin resistance. We investigated IRS-1–mediat...

BACKGROUND Insecticide treated nets (ITNs) and indoor residual spraying (IRS) are effective vector control tools that protect against malaria. There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone. This study investigated factors that may modify the effect of the combined use of IRS and ITNs compare...

Intracellular insulin signaling involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of SH2 domain signaling molecules that can interact with these substrates. In this study, we have evaluated the roles of IRS-1 and IRS-2 in signaling to the phosphatidylinositol (PI) 3-kinase pathway in the ob/ob mo...

OBJECTIVE SH2B1 is a SH2 domain-containing adaptor protein expressed in both the central nervous system and peripheral tissues. Neuronal SH2B1 controls body weight; however, the functions of peripheral SH2B1 remain unknown. Here, we studied peripheral SH2B1 regulation of insulin sensitivity and glucose metabolism. RESEARCH DESIGN AND METHODS We generated TgKO mice expressing SH2B1 in the brai...

The antiestrogens ICI 182,780 (ICI) and tamoxifen are clinically useful in the treatment of estrogen receptor-positive breast tumors. We assessed the in vivo effects of ICI, tamoxifen, and estradiol on the insulin-like growth factor (IGF) signaling pathway in the rat mammary gland. ICI significantly decreased the size of the lobular structures, Ki-67 labeling index, and insulin-like growth fact...

With increasing scale of Field Programmable Gate Arrays (FPGAs), architecture of interconnect resources (IRs) in FPGA is becoming more and more complicated. IR testing plays an important role to guarantee correct functionality of FPGAs. Usually, architecture of Global IRs is regular, while architecture of Local IRs is more complicated compared to Global IRs. In the paper, a generic IR model rev...

Insulin receptor substrates (IRS) serve as downstreammessengers from activated cell surface receptors to numerous signaling pathway cascades. One of these pathways, phosphoinositide 3-kinase (PI3K), frequently displays aberrant function in the setting of cancer. IRS proteins are capable of both regulating and activating PI3K, depending on the cell of origin. As such, both prohost and protumor f...