Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration
Top Cited Papers
- 11 February 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 287 (5455) , 1040-1046
- https://doi.org/10.1126/science.287.5455.1040
Abstract
Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kγ were generated. We show that PI3Kγ controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kγ-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)–coupled receptor (GPCR) agonists and chemotactic agents. PI3Kγ links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kγ regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.Keywords
This publication has 23 references indexed in Scilit:
- Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: A new intracellular signalling system?Published by Elsevier ,2003
- Signals involved in thymocyte positive and negative selectionSeminars in Immunology, 1999
- Requirement of Phosphatidylinositol 3-Kinase Activity for Bradykinin Stimulation of NF-κB Activation in Cultured Human Epithelial CellsPublished by Elsevier ,1999
- Xid -Like Immunodeficiency in Mice with Disruption of the p85α Subunit of Phosphoinositide 3-KinaseScience, 1999
- Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85αScience, 1999
- Phosphorylation and Activation of p70 s6k by PDK1Science, 1998
- Lipid-Regulated Kinases: Some Common Themes at LastScience, 1998
- Heterodimeric Phosphoinositide 3-Kinase Consisting of p85 and p110β Is Synergistically Activated by the βγ Subunits of G Proteins and Phosphotyrosyl PeptideJournal of Biological Chemistry, 1997
- Cloning and Characterization of a G Protein-Activated Human Phosphoinositide-3 KinaseScience, 1995
- Gene Therapy of the Immune SystemAnnual Review of Immunology, 1993