Trends in Immunology
Volume 28, Issue 2, February 2007, Pages 80-87
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Review
Antigen receptor signalling: a distinctive role for the p110δ isoform of PI3K

https://doi.org/10.1016/j.it.2006.12.007Get rights and content
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The activation of antigen receptors triggers two important signalling pathways originating from phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P2]. The first is phospholipase Cγ (PLCγ)-mediated hydrolysis of PtdIns(4,5)P2, resulting in the activation of Ras, protein kinase C and Ca2+ flux. This culminates in profound alterations in gene expression and effector-cell responses, including secretory granule exocytosis and cytokine production. By contrast, phosphoinositide 3-kinases (PI3Ks) phosphorylate PtdIns(4,5)P2 to yield phosphatidylinositol(3,4,5)-trisphosphate, activating signalling pathways that overlap with PLCγ or are PI3K-specific. Pathways that are PI3K-specific include Akt-mediated inactivation of Foxo transcription factors and transcription-independent regulation of glucose uptake and metabolism. The p110δ isoform of PI3K is the main source of PI3K activity following antigen recognition by B cells, T cells and mast cells. Here, we review the roles of p110δ in regulating antigen-dependent responses in these cell types.

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K.O. and B.V. are consultants for PIramed, UK.