NDLI: Recruitment of Sprouty1 to immune synapse regulates T cell receptor signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kim, In-Hoo Oh, Yu Mi Choi, Chung Yeon Choi, Heonsik Lee, Seung Hoon Lee, Ji Eun Lee, Jun Sung Park, Jong Bae Choi, Kyungho
Description	Author Affiliation: Lee JS ( Specific Organs Cancer Branch Research Institute National Cancer Center, Gyeonggi-do, Korea.)
Abstract	TCR stimulation not only initiates positive signals for T cell activation, but also induces negative signals that down-regulate T cells. We previously reported that Sprouty1, a negative regulator of Ras-MAPK pathway of receptor tyrosine kinases, was induced by TCR signal and inhibited TCR signaling in CD4+ T cell clones. In this study, we addressed the mechanism underlying Sprouty1 inhibition of T cells. When overexpressed in Jurkat T cells, Sprouty1 inhibited TCR signal-induced IL-2 transcription, and also AP-1, NFAT, and NF-kappaB activation, which suggests that Sprouty1 acts at proximal TCR signalosome. Accordingly, we found that Sprouty1 translocated to immune synapse upon TCR engagement in both Jurkat cells and activated primary T cells and interacted with various signaling molecules in the TCR signalosome, such as linker for activation of T cells (LAT), phospholipase C-gamma1 (PLC-gamma1), c-Cbl/Cbl-b, and HPK1. Sprouty1 inhibited LAT phosphorylation, leading to decreased MAPK activation and IL-2 production. Deletion of C-terminal 54 amino acids in Sprouty1 abolished its inhibitory effect and this deletion mutant was unable to translocate to immune synapse and interact with LAT. Overall, our data suggest that Sprouty1 induced by TCR signal negatively regulates further TCR signaling by interacting with proximal signaling molecules in immune synapse, providing a novel regulatory mechanism of T cells.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunological Synapses Immunology Membrane Proteins Phosphoproteins Receptors, Antigen, T-cell Signal Transduction T-lymphocytes Adaptor Proteins, Signal Transducing Animals Blotting, Western Gene Expression Gene Expression Regulation Metabolism Immunoprecipitation Interleukin-2 Biosynthesis Jurkat Cells Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Transgenic Microscopy, Confocal Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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