STAP-2 negatively regulates BCR-mediated B cell activation by recruiting tyrosine-protein kinase CSK to LYN

被引：1

作者：

Kashiwakura, Jun-ichi ^{[1
,2
,4
]}

Kawahara, Shoya ^{[1
]}

Inagaki, Iori ^{[1
]}

Inui, Kyosuke ^{[1
]}

Saitoh, Kodai ^{[1
]}

Kagohashi, Kota ^{[1
]}

Sasaki, Yuto ^{[1
]}

Kobayashi, Fuki ^{[1
]}

Kitai, Yuichi ^{[1
]}

Muromoto, Ryuta ^{[1
]}

Oritani, Kenji ^{[3
]}

Matsuda, Tadashi ^{[1
,5
]}

机构：

[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Sapporo, Hokkaido, Japan

[2] Hokkaido Univ Sci, Fac Pharmaceut Sci, Dept Life Sci, Sapporo, Hokkaido, Japan

[3] Int Univ Hlth & Welf, Dept Hematol, Chiba, Japan

[4] Hokkaido Univ Sci, Fac Pharmaceut Sci, Dept Life Sci, 15-4-1 Maeda 7 Jo,Teine Ku, Sapporo, Hokkaido 0068585, Japan

[5] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Kita 12 Nishi 6,Kita Ku, Sapporo, Hokkaido 0600812, Japan

来源：

FEBS LETTERS | 2023年 / 597卷 / 19期

关键词：

B cells; Csk; Lyn; signal-transducing adaptor protein-2; ANTIGEN RECEPTOR; DOWN-REGULATION; DEGRADATION; LYMPHOCYTES; ENDOCYTOSIS; INTERACTS;

D O I：

10.1002/1873-3468.14730

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：

Although signal-transducing adaptor protein-2 (STAP-2) acts in certain immune responses, its role in B cell receptor (BCR)-mediated signals remains unknown. In this study, we have revealed that BCR-mediated signals, cytokine production and antibody production were increased in STAP-2 knockout (KO) mice compared with wild-type (WT) mice. Phosphorylation of tyrosine-protein kinase LYN Y508 was reduced in STAP-2 KO B cells after BCR stimulation. Mechanistic analysis revealed that STAP-2 directly binds to LYN, dependently of STAP-2 Y250 phosphorylation by LYN. Furthermore, phosphorylation of STAP-2 enhanced interactions between LYN and tyrosine-protein kinase CSK, resulting in enhanced CSK-mediated LYN Y508 phosphorylation. These results suggest that STAP-2 is crucial for controlling BCR-mediated signals and antibody production by enhanced CSK-mediated feedback regulation of LYN.

引用

页码：2433 / 2445

页数：13

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