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BMC Cell Biology

, 7:10

First Online: 28 February 2006Received: 30 September 2005Accepted: 28 February 2006


BackgroundNotch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways.

ResultsWe show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells by the insulin pathway, in T-cells via TCR activation or in neurons via TrKB activation potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals.

ConclusionThe PI3K-Akt pathway acts as a -gain control- for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-7-10 contains supplementary material, which is available to authorized users.

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Autor: Grahame Mckenzie - George Ward - Yvette Stallwood - Emmanuel Briend - Sofia Papadia - Andrew Lennard - Martin Turner - Bria

Fuente: https://link.springer.com/article/10.1186/1471-2121-7-10

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