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• W1543342153 endingPage "1977" @default.
• W1543342153 startingPage "1969" @default.
• W1543342153 abstract "Abstract ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85α subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling. However, ICOS costimulation shows greater PI3K activity than CD28 in T cells. We show in this report that ICOS expression in activated T cells triggers the participation of p50α, one of the regulatory subunits of class IA PI3Ks. Using different T-APC cell conjugate systems, we report that p50α accumulates at the immunological synapse in activated but not in resting T cells. Our results demonstrate that ICOS membrane expression is involved in this process and that p50α plasma membrane accumulation requires a functional YMFM Src homology 2 domain-binding motif in ICOS. We also show that ICOS triggering with its ligand, ICOSL, induces the recruitment of p50α at the synapse of T cell/APC conjugates. In association with the p110 catalytic subunit, p50α is known to carry a stronger lipid kinase activity compared with p85α. Accordingly, we observed that ICOS engagement results in a stronger activation of PI3K. Together, these findings provide evidence that p50α is likely a determining factor in ICOS-mediated PI3K activity in T cells. These results also suggest that a differential recruitment and activity of class IA PI3K subunits represents a novel mechanism in the control of PI3K signaling by costimulatory molecules." @default.
• W1543342153 created "2016-06-24" @default.
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• W1543342153 date "2008-08-01" @default.
• W1543342153 modified "2023-10-14" @default.
• W1543342153 title "ICOS Ligation Recruits the p50α PI3K Regulatory Subunit to the Immunological Synapse" @default.
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• W1543342153 doi "https://doi.org/10.4049/jimmunol.181.3.1969" @default.
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