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

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Molecular Mechanisms of Human Disease Mediated by Oncogenic and Primary Immunodeficiency Mutations in Class IA Phosphoinositide 3-Kinases

The signaling lipid phosphatidylinositol 3,4,5, trisphosphate (PIP3) is an essential mediator of many vital cellular processes, including growth, survival, and metabolism. PIP3 is generated through the action of the class I phosphoinositide 3-kinases (PI3K), and their activity is tightly controlled through interactions with regulatory proteins and activating stimuli. The class IA PI3Ks are comp...

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Regulation of class IA PI3Ks: is there a role for monomeric PI3K subunits?

Class IA PI3Ks (phosphoinositide 3-kinases) consist of a p110 catalytic subunit bound to one of five regulatory subunits, known as p85s. Under unstimulated conditions, p85 stabilizes the labile p110 protein, while inhibiting its catalytic activity. Recruitment of the p85-p110 complex to receptors and adaptor proteins via the p85 SH2 (Src homology 2) domains alleviates this inhibition, leading t...

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The class IA isoforms of phosphoinositide 3-kinase (p110alpha, p110beta and p110delta) often have non-redundant functions in a given cell type. However, for reasons that are unclear, the role of a specific PI3K isoform can vary between cell types. Here, we compare the relative contributions of PI3K isoforms in primary and immortalised macrophages. In primary macrophages stimulated with the tyro...

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ژورنال

عنوان ژورنال: Biochemical Society Transactions

سال: 2020

ISSN: 0300-5127,1470-8752

DOI: 10.1042/bst20190845