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PI3K signaling through a biochemical systems lens

Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is best illustrated by the multifaceted nature of the many diseases associated with aberrant PI3K signaling, including common cancers,...

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Detalles Bibliográficos
Autores principales: Madsen, Ralitsa R., Toker, Alex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570132/
https://www.ncbi.nlm.nih.gov/pubmed/37673340
http://dx.doi.org/10.1016/j.jbc.2023.105224
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author Madsen, Ralitsa R.
Toker, Alex
author_facet Madsen, Ralitsa R.
Toker, Alex
author_sort Madsen, Ralitsa R.
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description Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is best illustrated by the multifaceted nature of the many diseases associated with aberrant PI3K signaling, including common cancers, metabolic disease, and rare developmental disorders. However, we are still far from a complete understanding of the fundamental control principles that govern the numerous phenotypic outputs that are elicited by activation of this well-characterized biochemical signaling network, downstream of an equally diverse set of extrinsic inputs. At its core, this is a question on the role of PI3K signaling in cellular information processing and decision making. Here, we review the determinants of accurate encoding and decoding of growth factor signals and discuss outstanding questions in the PI3K signal relay network. We emphasize the importance of quantitative biochemistry, in close integration with advances in single-cell time-resolved signaling measurements and mathematical modeling.
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spelling pubmed-105701322023-10-14 PI3K signaling through a biochemical systems lens Madsen, Ralitsa R. Toker, Alex J Biol Chem JBC Reviews Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is best illustrated by the multifaceted nature of the many diseases associated with aberrant PI3K signaling, including common cancers, metabolic disease, and rare developmental disorders. However, we are still far from a complete understanding of the fundamental control principles that govern the numerous phenotypic outputs that are elicited by activation of this well-characterized biochemical signaling network, downstream of an equally diverse set of extrinsic inputs. At its core, this is a question on the role of PI3K signaling in cellular information processing and decision making. Here, we review the determinants of accurate encoding and decoding of growth factor signals and discuss outstanding questions in the PI3K signal relay network. We emphasize the importance of quantitative biochemistry, in close integration with advances in single-cell time-resolved signaling measurements and mathematical modeling. American Society for Biochemistry and Molecular Biology 2023-09-09 /pmc/articles/PMC10570132/ /pubmed/37673340 http://dx.doi.org/10.1016/j.jbc.2023.105224 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle JBC Reviews
Madsen, Ralitsa R.
Toker, Alex
PI3K signaling through a biochemical systems lens
title PI3K signaling through a biochemical systems lens
title_full PI3K signaling through a biochemical systems lens
title_fullStr PI3K signaling through a biochemical systems lens
title_full_unstemmed PI3K signaling through a biochemical systems lens
title_short PI3K signaling through a biochemical systems lens
title_sort pi3k signaling through a biochemical systems lens
topic JBC Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570132/
https://www.ncbi.nlm.nih.gov/pubmed/37673340
http://dx.doi.org/10.1016/j.jbc.2023.105224
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