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Cracking the context-specific PI3K signaling code.

Madsen, RR; Vanhaesebroeck, B; (2020) Cracking the context-specific PI3K signaling code. Science Signaling , 13 (613) , Article eaay2940. 10.1126/scisignal.aay2940. Green open access

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Abstract

Specificity in signal transduction is determined by the ability of cells to “encode” and subsequently “decode” different environmental signals. Akin to computer software, this “signaling code” governs context-dependent execution of cellular programs through modulation of signaling dynamics and can be corrupted by disease-causing mutations. Class IA phosphoinositide 3-kinase (PI3K) signaling is critical for normal growth and development and is dysregulated in human disorders such as benign overgrowth syndromes, cancer, primary immune deficiency, and metabolic syndrome. Despite decades of PI3K research, understanding of context-dependent regulation of the PI3K pathway and of the underlying signaling code remains rudimentary. Here, we review current knowledge on context-specific PI3K signaling and how technological advances now make it possible to move from a qualitative to quantitative understanding of this pathway. Insight into how cellular PI3K signaling is encoded or decoded may open new avenues for rational pharmacological targeting of PI3K-associated diseases. The principles of PI3K context-dependent signal encoding and decoding described here are likely applicable to most, if not all, major cell signaling pathways.

Type: Article
Title: Cracking the context-specific PI3K signaling code.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scisignal.aay2940
Publisher version: http://dx.doi.org/10.1126/scisignal.aay2940
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10090167
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