Activation of the PI3K-AKT pathway in tumors is modulated by negative feedback, including mTORC1-mediated inhibition of upstream signaling. We now show that AKT inhibition induces the expression and phosphorylation of multiple receptor tyrosine kinases (RTKs). In a wide spectrum of tumor types, inhibition of AKT induces a conserved set of RTKs, including HER3, IGF-1R, and insulin receptor. This...

Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-...

The enzymatic activity of Bacillus subtilis glutamine synthetase (GS), which catalyzes the synthesis of glutamine from ammonium and glutamate, is regulated by glutamine feedback inhibition. The feedback-inhibited form of B. subtilis GS regulates the DNA-binding activities of the TnrA and GlnR nitrogen transcriptional factors. Bacterial GS proteins contain a flexible seven-residue loop, the Glu3...

THE FEEDBACK RESPONSE OF MEVALONATE: NADP oxidoreductase (acylating CoA; EC 1.1.1.34) in two varieties of hepatoma has been examined. In marked contrast to the feedback inhibition of this enzyme that is regularly observed in normal liver, the feedback control is completely lost in minimal-deviation hepatomas 9121 and 3924A. This finding provides the first specific biochemical localization of th...

Prostate cancer is characterized by its dependence on androgen receptor (AR) and frequent activation of PI3K signaling. We find that AR transcriptional output is decreased in human and murine tumors with PTEN deletion and that PI3K pathway inhibition activates AR signaling by relieving feedback inhibition of HER kinases. Similarly, AR inhibition activates AKT signaling by reducing levels of the...

in the present study the distribution of rubella hemagglutination inhibition (hi) antibody titer in the sera of 1486 women of 18 to 25 years old residing in tehran were examined. sera were pretreated with acid washed kaolin and pigeon red blood cell. titers below 1:10 and in some studies below 1:20 are considered nonimmune to rubella. our results show that 10, 29% of studied population had hi a...

The capacity of several purinethiol derivatives to produce prolongation of survival in mice bearing ascites-cell tumors and to produce feedback inhibition of purine synthesis in vivo in the tumor cells was investigated. Included were tumors susceptible and tumors resistant to treatment with 6-thioguanine. With susceptible tumors, certain of the purinethiols could increase survival of tumor-bear...

Antigen receptor allelic exclusion is thought to occur through mono-allelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into Vβ14 (Vβ14Rep) indicated that Vβ14 chromatin accessibility is bi-allelic. To determine whether Vβ14 recombinational accessibility is subject to fe...

Somatostatin (SST) is a peptide synthesized and released by a class of neostriatal local GABAergic interneurons, which, to some extent, are in charge of the feedforward inhibitory circuit. Spiny projection neurons (SPNs) make synapses with each other via their local axon collaterals, shaping the feedback inhibitory circuit. Both inhibitory circuits, feedforward and feedback, are related through...

Models of visual word recognition that have adopted an interactive activation framework (e.g., Coltheart, Curtis, Atkins, & Haller, 1993; Grainger & Jacobs, 1996) assume that activation can spread from semantic to orthographic representations via a feedback mechanism during visual word recognition. The present study used a mediated priming paradigm to test whether such feedback exists and, if s...