Antigen receptor signalling:: a distinctive role for the p110δ isoform of Pl3K

The activation of antigen receptors; triggers two important signalling pathways originating from phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P-2]. The first is phospholipase C gamma (PLC gamma) -mediated hydrolysis of PtdIns(4,5)P, 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 Ptdlns(4,5)P-2 to yield phosphatidylinositol (3,4,5)-trisphosphate, activating signalling pathways that overlap with PLCy 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 p110 delta 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 p110 delta in regulating antigen-dependent responses in these cell types.