共 42 条
Autoimmune-associated PTPN22 R620W Variation Reduces Phosphorylation of Lymphoid Phosphatase on an Inhibitory Tyrosine Residue
被引:80
作者:

Fiorillo, Edoardo
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h-index: 0
机构:
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Orru, Valeria
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h-index: 0
机构:
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Stanford, Stephanie M.
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h-index: 0
机构:
La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Liu, Yingge
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h-index: 0
机构:
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Salek, Mogjiborahman
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机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Rapini, Novella
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h-index: 0
机构:
Tor Vergata Univ, Dept Pediat, I-00133 Rome, Italy La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Schenone, Aaron D.
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h-index: 0
机构:
La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Saccucci, Patrizia
论文数: 0 引用数: 0
h-index: 0
机构:
Tor Vergata Univ, Dept Biopathol, I-00133 Rome, Italy La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Delogu, Lucia G.
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h-index: 0
机构:
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Angelini, Federica
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机构:
Tor Vergata Univ, Dept Pediat, I-00133 Rome, Italy La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Bitti, Maria Luisa Manca
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机构:
Tor Vergata Univ, Dept Pediat, I-00133 Rome, Italy La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Schmedt, Christian
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机构:
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Chan, Andrew C.
论文数: 0 引用数: 0
h-index: 0
机构:
Genentech Inc, Div Immunol, San Francisco, CA 94080 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Acuto, Oreste
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

Bottini, Nunzio
论文数: 0 引用数: 0
h-index: 0
机构:
La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA
Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA
机构:
[1] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA
[2] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA
[3] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[4] Tor Vergata Univ, Dept Pediat, I-00133 Rome, Italy
[5] Tor Vergata Univ, Dept Biopathol, I-00133 Rome, Italy
[6] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA
[7] Genentech Inc, Div Immunol, San Francisco, CA 94080 USA
基金:
美国国家卫生研究院;
关键词:
CELL ANTIGEN RECEPTOR;
TERMINAL SRC KINASE;
T-CELLS;
PROTEIN;
PHOSPHOTYROSINE;
ACTIVATION;
PEPTIDE;
VARIANT;
DOMAIN;
PEP;
D O I:
10.1074/jbc.M110.111104
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
A missense C1858T single nucleotide polymorphism in the PTPN22 gene recently emerged as a major risk factor for human autoimmunity. PTPN22 encodes the lymphoid tyrosine phosphatase (LYP), which forms a complex with the kinase Csk and is a critical negative regulator of signaling through the T cell receptor. The C1858T single nucleotide polymorphism results in the LYP-R620W variation within the LYP-Csk interaction motif. LYP-W620 exhibits a greatly reduced interaction with Csk and is a gain-of-function inhibitor of signaling. Here we show that LYP constitutively interacts with its substrate Lck in a Csk-dependent manner. T cell receptor-induced phosphorylation of LYP by Lck on an inhibitory tyrosine residue releases tonic inhibition of signaling by LYP. The R620W variation disrupts the interaction between Lck and LYP, leading to reduced phosphorylation of LYP, which ultimately contributes to gain-of-function inhibition of T cell signaling.
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收藏
页码:26506 / 26518
页数:13
相关论文
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Hungarian Acad Sci, Res Lab Pediat & Nephrol, Dept Pediat 1, H-1083 Budapest, Hungary
Semmelweis Univ, H-1083 Budapest, Hungary Univ Turku, Immunogenet Lab, MediCity Res Labs, FIN-20520 Turku, Finland

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机构: MCGILL UNIV,MCGILL CANC CTR,MONTREAL,PQ H3G 1Y6,CANADA
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Cloutier, JF
论文数: 0 引用数: 0
h-index: 0
机构: McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada

Veillette, A
论文数: 0 引用数: 0
h-index: 0
机构: McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada
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Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp
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Cohen, S
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Sick Children, Res Inst, Dept Paediat,Div Immunol & Allergy, Infect Immun Injury & Repair Programme, Toronto, ON M5G 1X8, Canada

Dadi, H
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机构: Hosp Sick Children, Res Inst, Dept Paediat,Div Immunol & Allergy, Infect Immun Injury & Repair Programme, Toronto, ON M5G 1X8, Canada

Shaoul, E
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Sick Children, Res Inst, Dept Paediat,Div Immunol & Allergy, Infect Immun Injury & Repair Programme, Toronto, ON M5G 1X8, Canada

Sharfe, N
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Sick Children, Res Inst, Dept Paediat,Div Immunol & Allergy, Infect Immun Injury & Repair Programme, Toronto, ON M5G 1X8, Canada

Roifman, CM
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Sick Children, Res Inst, Dept Paediat,Div Immunol & Allergy, Infect Immun Injury & Repair Programme, Toronto, ON M5G 1X8, Canada