期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 12, 页码 3165-3179出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20172018
关键词
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资金
- Public Health Service (PHS) [AI126845, AI095730]
- University of Pittsburgh
- PHS grant [AI103022, S10OD011925]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI103022, R21AI095730, R21AI126845] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD011925] Funding Source: NIH RePORTER
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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