Impaired B and T cell antigen receptor signaling in p110δ PI 3-kinase mutant mice

K Okkenhaug, A Bilancio, G Farjot, H Priddle, S Sancho… - Science, 2002 - science.org
K Okkenhaug, A Bilancio, G Farjot, H Priddle, S Sancho, E Peskett, W Pearce, SE Meek…
Science, 2002science.org
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 …
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.
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