Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K.
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 Cgamma (PLCgamma)-mediated hydrolysis of PtdIns(4,5)P(2), resulting in the activation of Ras, protein kinase C and Ca(2+) 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)P(2) to yield phosphatidylinositol(3,4,5)-trisphosphate, activating signalling pathways that overlap with PLCgamma 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 p110delta 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 p110delta in regulating antigen-dependent responses in these cell types.
Okkenhaug
Klaus
K
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK, CB2 4AT. klaus.okkenhaug@bbsrc.ac.uk
Ali
Khaled
K
Vanhaesebroeck
Bart
B
D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D011946:Receptors, Antigen / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D021122:Protein Subunits; D011946:Receptors, Antigen; D019869:Phosphatidylinositol 3-Kinases