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Class IA PI3K regulatory subunits: p110-independent roles and structures

The phosphatidylinositol 3-kinase (PI3K) pathway is a critical regulator of many cellular processes including cell survival, growth, proliferation and motility. Not surprisingly therefore, the PI3K pathway is one of the most frequently mutated pathways in human cancers. In addition to their canonica...

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Detalles Bibliográficos
Autores principales: Fox, Millie, Mott, Helen R., Owen, Darerca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458397/
https://www.ncbi.nlm.nih.gov/pubmed/32677674
http://dx.doi.org/10.1042/BST20190845
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author Fox, Millie
Mott, Helen R.
Owen, Darerca
author_facet Fox, Millie
Mott, Helen R.
Owen, Darerca
author_sort Fox, Millie
collection PubMed
description The phosphatidylinositol 3-kinase (PI3K) pathway is a critical regulator of many cellular processes including cell survival, growth, proliferation and motility. Not surprisingly therefore, the PI3K pathway is one of the most frequently mutated pathways in human cancers. In addition to their canonical role as part of the PI3K holoenzyme, the class IA PI3K regulatory subunits undertake critical functions independent of PI3K. The PI3K regulatory subunits exist in excess over the p110 catalytic subunits and therefore free in the cell. p110-independent p85 is unstable and exists in a monomer-dimer equilibrium. Two conformations of dimeric p85 have been reported that are mediated by N-terminal and C-terminal protein domain interactions, respectively. The role of p110-independent p85 is under investigation and it has been found to perform critical adaptor functions, sequestering or influencing compartmentalisation of key signalling proteins. Free p85 has roles in glucose homeostasis, cellular stress pathways, receptor trafficking and cell migration. As a regulator of fundamental pathways, the amount of p110-independent p85 in the cell is critical. Factors that influence the monomer-dimer equilibrium of p110-independent p85 offer additional control over this system, disruption to which likely results in disease. Here we review the current knowledge of the structure and functions of p110-independent class IA PI3K regulatory subunits.
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spelling pubmed-74583972020-09-04 Class IA PI3K regulatory subunits: p110-independent roles and structures Fox, Millie Mott, Helen R. Owen, Darerca Biochem Soc Trans Review Articles The phosphatidylinositol 3-kinase (PI3K) pathway is a critical regulator of many cellular processes including cell survival, growth, proliferation and motility. Not surprisingly therefore, the PI3K pathway is one of the most frequently mutated pathways in human cancers. In addition to their canonical role as part of the PI3K holoenzyme, the class IA PI3K regulatory subunits undertake critical functions independent of PI3K. The PI3K regulatory subunits exist in excess over the p110 catalytic subunits and therefore free in the cell. p110-independent p85 is unstable and exists in a monomer-dimer equilibrium. Two conformations of dimeric p85 have been reported that are mediated by N-terminal and C-terminal protein domain interactions, respectively. The role of p110-independent p85 is under investigation and it has been found to perform critical adaptor functions, sequestering or influencing compartmentalisation of key signalling proteins. Free p85 has roles in glucose homeostasis, cellular stress pathways, receptor trafficking and cell migration. As a regulator of fundamental pathways, the amount of p110-independent p85 in the cell is critical. Factors that influence the monomer-dimer equilibrium of p110-independent p85 offer additional control over this system, disruption to which likely results in disease. Here we review the current knowledge of the structure and functions of p110-independent class IA PI3K regulatory subunits. Portland Press Ltd. 2020-08-28 2020-07-17 /pmc/articles/PMC7458397/ /pubmed/32677674 http://dx.doi.org/10.1042/BST20190845 Text en © 2020 The Author(s) https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University of Cambridge in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.
spellingShingle Review Articles
Fox, Millie
Mott, Helen R.
Owen, Darerca
Class IA PI3K regulatory subunits: p110-independent roles and structures
title Class IA PI3K regulatory subunits: p110-independent roles and structures
title_full Class IA PI3K regulatory subunits: p110-independent roles and structures
title_fullStr Class IA PI3K regulatory subunits: p110-independent roles and structures
title_full_unstemmed Class IA PI3K regulatory subunits: p110-independent roles and structures
title_short Class IA PI3K regulatory subunits: p110-independent roles and structures
title_sort class ia pi3k regulatory subunits: p110-independent roles and structures
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458397/
https://www.ncbi.nlm.nih.gov/pubmed/32677674
http://dx.doi.org/10.1042/BST20190845
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