Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration.
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 PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma-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. PI3Kgamma 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, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.
Sasaki
T
T
Amgen Institute, 620 University Avenue, Toronto M5G 2C1, Ontario, Canada.
Irie-Sasaki
J
J
Jones
R G
RG
Oliveira-dos-Santos
A J
AJ
Stanford
W L
WL
Bolon
B
B
Wakeham
A
A
Itie
A
A
Bouchard
D
D
Kozieradzki
I
I
Joza
N
N
Mak
T W
TW
Ohashi
P S
PS
Suzuki
A
A
Penninger
J M
JM
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016897:Respiratory Burst; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D002630:Chemotactic Factors; D020962:Heterotrimeric GTP-Binding Proteins; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C060974:phosphatidylinositol 3,4,5-triphosphate