Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation.

Abstract:

:Phosphoinositide 3-kinase (PI3K) defines a family of lipid kinases that direct a wide range of cellular processes and cell fate decisions. Since its discovery, and that of its enzymatic antagonist PTEN, much of the focus on PI3K has been on its oncogenic potential. In recent years, studies on PI3K signaling in B lymphocytes have established the importance of this pathway in effecting B cell differentiation and associated molecular events such as V(D)J recombination and class switch recombination. Intriguing new findings also indicate that there is specificity in the PI3K pathway in B cells, including preferential expression or usage of particular PI3K isoforms and counter-regulation by the PTEN and SHIP phosphatases. The role of PI3K adaptor proteins (CD19, BCAP, and TC21) has also undergone revision to reflect both shared and unique properties. The emergence of Foxo1 as a critical PI3K regulatory target for B cell differentiation has united membrane proximal regulatory events orchestrated by PI3K/PTEN/SHIP with key transcriptional targets. Insights into the regulation and impact of PI3K signaling have been brought to bear in new treatments for B cell malignancies, and will also be an important topic of consideration for B cell-dependent autoimmune diseases.

journal_name

Curr Opin Immunol

authors

Baracho GV,Miletic AV,Omori SA,Cato MH,Rickert RC

doi

10.1016/j.coi.2011.01.001

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

178-83

issue

2

eissn

0952-7915

issn

1879-0372

pii

S0952-7915(11)00002-1

journal_volume

23

pub_type

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