Publication Date:
2000-02-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, T -- Irie-Sasaki, J -- Jones, R G -- Oliveira-dos-Santos, A J -- Stanford, W L -- Bolon, B -- Wakeham, A -- Itie, A -- Bouchard, D -- Kozieradzki, I -- Joza, N -- Mak, T W -- Ohashi, P S -- Suzuki, A -- Penninger, J M -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1040-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, 620 University Avenue, Toronto M5G 2C1, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669416" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/analysis
;
Apoptosis
;
Cell Line
;
Chemotactic Factors/pharmacology
;
Chemotaxis, Leukocyte/*physiology
;
Heterotrimeric GTP-Binding Proteins/metabolism
;
Lymph Nodes/cytology
;
*Lymphocyte Activation
;
Mice
;
Mice, Knockout
;
Mitogen-Activated Protein Kinases/metabolism
;
Neutrophils/*physiology
;
Peritonitis/immunology
;
Phosphatidylinositol 3-Kinases/*metabolism
;
Phosphatidylinositol Phosphates/metabolism
;
*Protein-Serine-Threonine Kinases
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-akt
;
Respiratory Burst
;
Signal Transduction
;
Spleen/cytology
;
T-Lymphocytes/cytology/*immunology
;
Thymus Gland/*cytology/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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