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

• Published in: FEBS letters Vol. 597; no. 19; pp. 2433 - 2445
• Main Authors: Kashiwakura, Jun‐ichi, Kawahara, Shoya, Inagaki, Iori, Inui, Kyosuke, Saitoh, Kodai, Kagohashi, Kota, Sasaki, Yuto, Kobayashi, Fuki, Kitai, Yuichi, Muromoto, Ryuta, Oritani, Kenji, Matsuda, Tadashi
• Format: Journal Article
• Language: English
• Published: 01.10.2023
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14730

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.