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

共 38 条

[11] STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation [J].

Ikeda, Osamu ;

Miyasaka, Yuto ;

Sekine, Yuichi ;

Mizushima, Akihiro ;

Muromoto, Ryuta ;

Nanbo, Asuka ;

Yoshimura, Akihiko ;

Matsuda, Tadashi .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 384 (01) :71-75

[12] Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells [J].

Ingley, Evan ;

Schneider, Jessica R. ;

Payne, Christine J. ;

McCarthy, David J. ;

Harder, Kenneth W. ;

Hibbs, Margaret L. ;

Klinken, S. Peter .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (42) :31920-31929

[13] LAB: A new membrane-associated adaptor molecule in B cell activation [J].

Janssen, E ;

Zhu, MH ;

Zhang, WJ ;

Koonpaew, S ;

Zhang, WG .

NATURE IMMUNOLOGY, 2003, 4 (02) :117-123

[14] STAP-2 positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions [J].

Kashiwakura, Jun-ichi ;

Yamashita, Shinsuke ;

Yoshihara, Mari ;

Inui, Kyosuke ;

Saitoh, Kodai ;

Sekine, Yuichi ;

Muromoto, Ryuta ;

Kitai, Yuichi ;

Oritani, Kenji ;

Matsuda, Tadashi .

INTERNATIONAL IMMUNOLOGY, 2019, 31 (05) :349-356

[15] Nasal Sensitization with Ragweed Pollen Induces Local-Allergic-Rhinitis-Like Symptoms in Mice [J].

Kato, Yukinori ;

Akasaki, Shoko ;

Muto-Haenuki, Yoko ;

Fujieda, Shigeharu ;

Matsushita, Kazufumi ;

Yoshimoto, Tomohiro .

PLOS ONE, 2014, 9 (08)

[16] Improved Phos-tag SDS-PAGE under neutral pH conditions for advanced protein phosphorylation profiling [J].

Kinoshita, Eiji ;

Kinoshita-Kikuta, Emiko .

PROTEOMICS, 2011, 11 (02) :319-323

[17] ROLE OF THE SYK AUTOPHOSPHORYLATION SITE AND SH2 DOMAINS IN B-CELL ANTIGEN RECEPTOR SIGNALING [J].

KUROSAKI, T ;

JOHNSON, SA ;

PAO, L ;

SADA, K ;

YAMAMURA, H ;

CAMBIER, JC .

JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1815-1823

[18] B-CELL ANTIGEN RECEPTOR MOTIFS HAVE REDUNDANT SIGNALING CAPABILITIES AND BIND THE TYROSINE KINASES PTK72, LYN AND FYN [J].

LAW, DA ;

CHAN, VWF ;

DATTA, SK ;

DEFRANCO, AL .

CURRENT BIOLOGY, 1993, 3 (10) :645-657

[19] CROSS-LINKING OF SURFACE-IMMUNOGLOBULIN ACTIVATES SRC-RELATED TYROSINE KINASES IN WEHI-231 CELLS [J].

LI, ZH ;

MAHAJAN, S ;

PRENDERGAST, MM ;

FARGNOLI, J ;

ZHU, XY ;

KLAGES, S ;

ADAM, D ;

SCHIEVEN, GL ;

BLAKE, J ;

BOLEN, JB ;

BURKHARDT, AL .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 187 (03) :1536-1544

[20] STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif [J].

Minoguchi, M ;

Minoguchi, S ;

Aki, D ;

Joo, A ;

Yamamoto, T ;

Yumioka, T ;

Matsuda, T ;

Yoshimura, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) :11182-11189

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