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 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / analysis
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Apoptosis
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Cell Line
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Chemotactic Factors / pharmacology
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Chemotaxis, Leukocyte / physiology*
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Heterotrimeric GTP-Binding Proteins / metabolism
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Lymph Nodes / cytology
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Lymphocyte Activation*
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Neutrophils / physiology*
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Peritonitis / immunology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol Phosphates / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Respiratory Burst
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Signal Transduction
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Spleen / cytology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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Thymus Gland / cytology*
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Thymus Gland / immunology
Substances
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Antigens, CD
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Chemotactic Factors
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Phosphatidylinositol Phosphates
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Proto-Oncogene Proteins
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phosphatidylinositol 3,4,5-triphosphate
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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Heterotrimeric GTP-Binding Proteins