Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice
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- 9 August 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 297 (5583) , 1031-1034
- https://doi.org/10.1126/science.1073560
Abstract
Class IA phosphoinositide 3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that generate second messenger signals downstream of tyrosine kinases, thereby controlling cell metabolism, growth, proliferation, differentiation, motility, and survival. Mammals express three class IA catalytic subunits: p110α, p110β, and p110δ. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110δ (p110δD910A) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110δ mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110δ in immunity.Keywords
This publication has 21 references indexed in Scilit:
- T Cell MemoryAnnual Review of Immunology, 2002
- Phosphoinositide 3-kinase in immunological systemsSeminars in Immunology, 2002
- Cellular Function of Phosphoinositide 3-Kinases: Implications for Development, Immunity, Homeostasis, and CancerAnnual Review of Cell and Developmental Biology, 2001
- Synthesis and Function of 3-Phosphorylated Inositol LipidsAnnual Review of Biochemistry, 2001
- Impaired Kit- but Not FcεRI-initiated Mast Cell Activation in the Absence of Phosphoinositide 3-Kinase p85α Gene ProductsJournal of Biological Chemistry, 2000
- Proliferative Defect and Embryonic Lethality in Mice Homozygous for a Deletion in the p110α Subunit of Phosphoinositide 3-KinaseJournal of Biological Chemistry, 1999
- Xid -Like Immunodeficiency in Mice with Disruption of the p85α Subunit of Phosphoinositide 3-KinaseScience, 1999
- Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85αScience, 1999
- PtdIns-3,4,5-P3Cell, 1998
- Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in VivoScience, 1990