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Open AccessJournal ArticleDOI

Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells

Klaus Okkenhaug
- 21 Mar 2013 - 
- Vol. 31, Iss: 1, pp 675-704
TLDR
The understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular.
Abstract
Phosphoinositide 3-kinases (PI3Ks) control many important aspects of immune cell development, differentiation, and function. Mammals have eight PI3K catalytic subunits that are divided into three classes based on similarities in structure and function. Specific roles for the class I PI3Ks have been broadly investigated and are relatively well understood, as is the function of their corresponding phosphatases. More recently, specific roles for the class II and class III PI3Ks have emerged. Through vertebrate evolution and in parallel with the evolution of adaptive immunity, there has been a dramatic increase not only in the genes for PI3K subunits but also in genes for phosphatases that act on 3-phosphoinositides and in 3-phosphoinositide-binding proteins. Our understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular.

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Journal ArticleDOI

The PI3K pathway in human disease

TL;DR: A perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions is provided, two topics closely intertwined with cancer biology.
Journal ArticleDOI

PI3K and cancer: lessons, challenges and opportunities

TL;DR: Through a greater focus on patient selection, increased understanding of immune modulation and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anticancer agents.
Journal ArticleDOI

Targeting PI3K in cancer: mechanisms and advances in clinical trials

TL;DR: A critical review is performed to summarize the role of the PI3K pathway in tumor development, recentPI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3k inhibition.
Journal ArticleDOI

Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage

TL;DR: Activated PI3K-δ syndrome (APDS), a PID associated with a dominant gain-of-function mutation in which lysine replaced glutamic acid at residue 1021 (E1021K) in the p110δ protein, the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), encoded by the PIK3CD gene is described.
Journal ArticleDOI

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer

TL;DR: It is reported that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours, and can break tumour-induced immune tolerance and should be considered for wider use in oncology.
References
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Journal ArticleDOI

Guidelines for the use and interpretation of assays for monitoring autophagy

Daniel J. Klionsky, +1287 more
- 01 Apr 2012 - 
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
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