Context. IRAS 20343+4129 was suggested to harbor one of the most massive and embedded stars in the Cygnus OB2 association, IRS 1, which seemed to be associated with a north-south molecular outflow. However, the dust emission peaks do not coincide with the position of IRS 1, but lie on either side of another massive Young Stellar Object (YSO), IRS 3, which is associated with centimeter emission....

Activation of tyrosine kinases by numerous growth factor and cytokine receptors leads to tyrosine phosphorylation of the insulin receptor substrate (IRS)-proteins. Tyrosine-phosphorylated motifs on the IRS proteins bind to the SH2 domains in proteins that mediate downstream signals, including phosphatidylinositol 3'-kinase, GRB-2, and SHP-2. We investigated the function of the two SHP-2 binding...

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...

The receptor for insulin-like growth factor I (IGF-IR) controls normal and pathological growth of cells. DNA repair pathways represent an unexplored target through which the IGF-IR signaling system might support pathological growth leading to cellular transformation. However, this study demonstrates that IGF-I stimulation supports homologous recombination-directed DNA repair (HRR). This effect ...

Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin e...

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...

OBJECTIVE Appropriate regulation of insulin receptor substrate 2 (IRS-2) expression in pancreatic β-cells is essential to adequately compensate for insulin resistance. In liver, basal IRS-2 expression is controlled via a temporal negative feedback of sterol regulatory element-binding protein 1 (SREBP-1) to antagonize transcription factors forkhead box class O (FoxO)1/FoxO3a at an insulin respon...

Interleukins 9 (IL-9) and 4 are cytokines within the IL-2 receptor gamma chain (IL-2R gamma) superfamily that possess similar and unique biological functions. The signaling mechanisms, which may determine cytokine specificity and redundancy, are not well understood. IRS proteins are tyrosine-phosphorylated following IL-9 and IL-4 stimulation, a process in part mediated by JAK tyrosine kinases (...

Pleckstrin homology (PH) domains occur in many signaling proteins, including substrates for the insulin receptor tyrosine kinase (IRS proteins). Based on the hypothesis that PH domains may have a common function such as membrane targeting we tested the ability of PH domains from other signaling molecules to link IRS-1 to the insulin receptor. Chimeric IRS-1 proteins containing a homologous PH d...