The P85beta Regulatory Subunit of Phosphoinositide 3-kinase Has Unique and Redundant Functions in B Cells

Overview

Journal Autoimmunity

Specialty Allergy & Immunology

Date 2009 Oct 9

PMID 19811262

Citations 10

Authors

Jean S Oak

Jing Chen

Raechel Q Peralta

Jonathan A Deane

David A Fruman

Affiliations

Soon will be listed here.

Abstract

Phosphoinositide kinase (PI3K) is activated by various receptors on lymphocytes and regulates development, activation, and tolerance. Genetic ablation of PI3K function in T cells leads to the appearance of autoimmune disorders. In B cells, loss of the class IA regulatory subunit p85alpha causes a partial defect in B cell development and proliferation, whereas loss of p85beta alone causes no apparent changes in B cell function. Here we investigate further the consequences of p85beta deletion in B cells, in the presence or absence of p85alpha. We demonstrate that p85beta partially compensates for loss of p85alpha in B cell development and peripheral survival, with greater defects observed when both isoforms are absent. BCR-mediated AKT phosphorylation is partially reduced in p85alpha-deficient B cells and further diminished with concomitant loss of p85beta. Unexpectedly, loss of p85beta results in increased BCR-mediated proliferation and ERK phosphorylation. These results indicate that the p85beta regulatory isoform has partially overlapping functions with p85alpha in B cells as well as a unique role in opposing BCR responses.

Citing Articles

Divergent roles of the regulatory subunits of class IA PI3K.

Kim C, Lee J, Park S Front Endocrinol (Lausanne). 2024; 14:1152579.

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Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction.

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The regulatory subunits of PI3K, p85α and p85β, differentially affect BRD7-mediated regulation of insulin signaling.

Lee J, Liu R, Park S J Mol Cell Biol. 2021; 13(12):889-901.

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Quantitation of class IA PI3Ks in mice reveals p110-free-p85s and isoform-selective subunit associations and recruitment to receptors.

Tsolakos N, Durrant T, Chessa T, Suire S, Oxley D, Kulkarni S Proc Natl Acad Sci U S A. 2018; 115(48):12176-12181.

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Isoform-specific activities of the regulatory subunits of phosphatidylinositol 3-kinases - potentially novel therapeutic targets.

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