RT Journal Article
SR Electronic
T1 Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1040
OP 1046
DO 10.1126/science.287.5455.1040
VO 287
IS 5455
A1 Sasaki, Takehiko
A1 Irie-Sasaki, Junko
A1 Jones, Russell G.
A1 Oliveira-dos-Santos, Antonio J.
A1 Stanford, William L.
A1 Bolon, Brad
A1 Wakeham, Andrew
A1 Itie, Annick
A1 Bouchard, Dennis
A1 Kozieradzki, Ivona
A1 Joza, Nicholas
A1 Mak, Tak W.
A1 Ohashi, Pamela S.
A1 Suzuki, Akira
A1 Penninger, Josef M.
YR 2000
UL http://science.sciencemag.org/content/287/5455/1040.abstract
AB 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.