Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice |
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Authors: | Okkenhaug Klaus Bilancio Antonio Farjot Géraldine Priddle Helen Sancho Sara Peskett Emma Pearce Wayne Meek Stephen E Salpekar Ashreena Waterfield Michael D Smith Andrew J H Vanhaesebroeck Bart |
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Affiliation: | Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK. |
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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: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity. |
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