PI3K in lymphocyte development, differentiation and activation View Full Text


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Article Info

DATE

2003-04

AUTHORS

Klaus Okkenhaug, Bart Vanhaesebroeck

ABSTRACT

Key PointsRecent mouse-knockout experiments have indicated crucial, non-redundant functions for individual phosphoinositide 3-kinase (PI3K) subunits. p85α and p110δ have crucial roles in B-cell development, differentiation and function. p110δ, but not p85α, has an important role in T-cell activation and differentiation. p110γ regulates innate immunity and T-cell activation, but it is not clear what extracellular stimuli regulate p110γ in T cells. CD5+ B1 cells and marginal-zone B cells do not develop in the absence of PI3K activity. Recruitment of PI3K by the T-cell co-stimulatory receptor CD28 seems to have a selective role in the regulation of cell survival, but not in proliferation or interleukin-2 production. Unrestrained PI3K signalling, caused by the lack of expression of SH2-domain-containing inositol polyphosphate D5 phosphatase (SHIP) or phosphatase and tensin homologue (PTEN), can lead to autoimmune disease and/or leukaemia. The phenotypes of p110δ- and p110γ-deficient mice indicate that these subunits are attractive drug targets for the alleviation of autoimmune diseases. More... »

PAGES

317-330

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    49 schema:description Key PointsRecent mouse-knockout experiments have indicated crucial, non-redundant functions for individual phosphoinositide 3-kinase (PI3K) subunits. p85α and p110δ have crucial roles in B-cell development, differentiation and function. p110δ, but not p85α, has an important role in T-cell activation and differentiation. p110γ regulates innate immunity and T-cell activation, but it is not clear what extracellular stimuli regulate p110γ in T cells. CD5+ B1 cells and marginal-zone B cells do not develop in the absence of PI3K activity. Recruitment of PI3K by the T-cell co-stimulatory receptor CD28 seems to have a selective role in the regulation of cell survival, but not in proliferation or interleukin-2 production. Unrestrained PI3K signalling, caused by the lack of expression of SH2-domain-containing inositol polyphosphate D5 phosphatase (SHIP) or phosphatase and tensin homologue (PTEN), can lead to autoimmune disease and/or leukaemia. The phenotypes of p110δ- and p110γ-deficient mice indicate that these subunits are attractive drug targets for the alleviation of autoimmune diseases.
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    64 PointsRecent mouse-knockout experiments
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    66 Unrestrained PI3K
    67 absence
    68 activation
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