Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration

• Published in: Science (American Association for the Advancement of Science) 2000-02, Vol.287 (5455), p.1040-1046
• Main Authors: Sasaki, Takehiko, Irie-Sasaki, Junko, Jones, Russell G., Antonio J. Oliveira-dos-Santos, Stanford, William L., Bolon, Brad, Wakeham, Andrew, Itie, Annick, Bouchard, Dennis, Kozieradzki, Ivona, Joza, Nicholas, Mak, Tak W., Ohashi, Pamela S., Suzuki, Akira, Penninger, Josef M.
• Format: Article
• Language: English
• Subjects: Apoptosis; B lymphocytes; Biological and medical sciences; Cell lines; Cell physiology; Chemotaxis; Fundamental and applied biological sciences. Psychology; Mice; Molecular and cellular biology; Neutrophils; Receptors; Signal transduction; Spleen; T lymphocytes; Thymocytes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.287.5455.1040

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.