THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1

Choi Seeyoung; Warzecha Claude; Zvezdova Ekaterina; Lee Jan; Argenty Jeremy; Lesourne Renaud; Aravind L.; Love Paul E.

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THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1

机译：主题增强TCR信号，并通过选择性抑制磷酸酶SHP-1来实现阳性选择

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THEMIS, a T cell-specific protein with high expression in CD4(+)CD8(+) thymocytes, has a crucial role in positive selection and T cell development. THEMIS lacks defined catalytic domains but contains two tandem repeats of a distinctive module of unknown function (CABIT). Here we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1. This action was mediated by the CABIT modules, which bound to the phosphatase domain of SHP-1 and promoted or stabilized oxidation of SHP-1's catalytic cysteine residue, which inhibited the tyrosine-phosphatase activity of SHP-1. Deletion of SHP-1 alleviated the developmental block in Themis(-/-) thymocytes. Thus, THEMIS facilitates thymocyte positive selection by enhancing the T cell antigen receptor signaling response to low-affinity ligands.

机译：Themis是CD4（+）CD8（+）胸腺细胞高表达的T细胞特异性蛋白质，具有至关重要的作用，在阳性选择和T细胞发育中作用。主题缺乏定义的催化畴，但包含两个未知功能模块的两个串联重复（Cabit）。在这里，我们发现主题直接调节酪氨酸磷酸酶SHP-1的催化活性。该动作是由Cabit模块介导的，其与SHP-1的磷酸酶结构域结合并促进或稳定的SHP-1催化半胱氨酸残基的氧化，这抑制了SHP-1的酪氨酸 - 磷酸酶活性。 SHP-1删除减轻了题目（ - / - ）胸腺细胞的发育块。因此，通过增强对低亲和力配体的T细胞抗原受体信号传导反应来促进胸腺细胞阳性选择。

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《Nature immunology》 |2017年第4期|共10页
作者
Choi Seeyoung; Warzecha Claude; Zvezdova Ekaterina; Lee Jan; Argenty Jeremy; Lesourne Renaud; Aravind L.; Love Paul E.;
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作者单位

Eunice Kennedy Shriver Natl Inst Child Hlth &

Hum Sect Hematopoiesis &

Lymphocyte Biol NIH;

Eunice Kennedy Shriver Natl Inst Child Hlth &

Hum Sect Hematopoiesis &

Lymphocyte Biol NIH;

Eunice Kennedy Shriver Natl Inst Child Hlth &

Hum Sect Hematopoiesis &

Lymphocyte Biol NIH;

Eunice Kennedy Shriver Natl Inst Child Hlth &

Hum Sect Hematopoiesis &

Lymphocyte Biol NIH;

Ctr Physiopathol Toulouse Purpan Toulouse France;

Ctr Physiopathol Toulouse Purpan Toulouse France;

NIH Natl Lib Med Bldg 10 Bethesda MD 20892 USA;

Eunice Kennedy Shriver Natl Inst Child Hlth &

Hum Sect Hematopoiesis &

Lymphocyte Biol NIH;

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正文语种 eng
中图分类医学免疫学;
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1. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1 (vol 18, pg 433, 2017) [J] . Choi Seeyoung, Warzecha Claude, Zvezdova Ekaterina, Journal of Turbulence . 2017,第6期

机译：主题增强TCR信号，通过选择性抑制磷酸酶SHP-1（Vol 18，PG 433,2017）来实现阳性选择。
2. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1 (vol 18, pg 433, 2017) [J] . Choi Seeyoung, Warzecha Claude, Zvezdova Ekaterina, Nature immunology . 2017,第6期

机译：主题增强TCR信号，通过选择性抑制磷酸酶SHP-1（Vol 18，PG 433,2017）来实现阳性选择。
3. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1 [J] . Choi Seeyoung, Warzecha Claude, Zvezdova Ekaterina, Nature immunology . 2017,第4期

机译：主题增强TCR信号，并通过选择性抑制磷酸酶SHP-1来实现阳性选择
4. Nanoparticles Coated with Frizzled7 Antibodies Enable Multivalent Binding for Enhanced Wnt Signaling Inhibition in Triple-Negative Breast Cancer [C] . Rachel S. Riley, Emily S. Day Society for Biomaterials annual meeting and exposition . 2018

机译：纳米颗粒涂有Frizzled7抗体使三价乳腺癌中增强Wnt信号抑制的多价结合。
5. The protein tyrosine phosphatase SHP-1 sets signaling thresholds during thymocyte development. [D] . Carter, Jennifer Dawn. 2003

机译：酪氨酸磷酸酶SHP-1蛋白可在胸腺细胞发育过程中设定信号转导阈值。
6. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of SHP-1 [O] . Seeyoung Choi, Claude Warzecha, Ekaterina Zvezdova, -1

机译：THEMIS增强TCR信号传导并通过选择性抑制SHP-1进行阳性选择
7. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1 [O] . Seeyoung Choi, Claude Warzecha, Ekaterina Zvezdova, 2017

机译：主题增强TCR信号，并通过选择性抑制磷酸酶SHP-1来实现阳性选择
8. Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines [R] . Levitt, J. M. 2009

机译：在树突状细胞中抑制蛋白酪氨酸磷酸酶sHp-1以增强其作为基于细胞的前列腺癌疫苗的功效

THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1

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