PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt.
PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt.
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DOI：
10.1084/jem.20172018
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发表时间：
2018-12-03
期刊：
影响因子：
--
通讯作者：
Kane LP
中科院分区：
文献类型：
--
作者：
Uche UU;Piccirillo AR;Kataoka S;Grebinoski SJ;D'Cruz LM;Kane LP
This study demonstrates a role for the transmembrane regulator of PI3K (TrIP) in restricting early T cell activation, at least in part through effects on PI3K. It is also shown that levels of TrIP decrease preceding full T cell activation. Phosphatidylinositol-3 kinases (PI3Ks) modulate cellular growth, proliferation, and survival; dysregulation of the PI3K pathway can lead to autoimmune disease and cancer. PIK3IP1 (or transmembrane inhibitor of PI3K [TrIP]) is a putative transmembrane regulator of PI3K. TrIP contains an extracellular kringle domain and an intracellular domain with homology to the inter-SH2 domain of the PI3K regulatory subunit p85, but the mechanism of TrIP function is poorly understood. We show that both the kringle and p85-like domains are necessary for TrIP inhibition of PI3K and that TrIP is down-modulated from the surface of T cells during T cell activation. In addition, we present evidence that the kringle domain may modulate TrIP function by mediating oligomerization. Using an inducible knockout mouse model, we show that TrIP-deficient T cells exhibit more robust activation and can mediate clearance of Listeria monocytogenes infection faster than WT mice. Thus, TrIP is a negative regulator of T cell activation and may represent a novel target for immune modulation.
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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通讯作者：
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