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

In this study, the role of STAP-2 in B cell functions was analyzed. BCR-mediated B cell activation was enhanced in STAP-2 KO mice by inhibiting recruitment of Csk to Lyn. In accordance with the results, antibody production was significantly higher in STAP-2 KO mice compared with WT mice. Therefore, STAP-2 is important for the regulation of BCR signaling in B cells. 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 inSTAP-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.

Source: FEBS Letters - October 9, 2023 Category: Biochemistry Authors: Jun ‐ichi Kashiwakura, Shoya Kawahara, Iori Inagaki, Kyosuke Inui, Kodai Saitoh, Kota Kagohashi, Yuto Sasaki, Fuki Kobayashi, Yuichi Kitai, Ryuta Muromoto, Kenji Oritani, Tadashi Matsuda Tags: Research Letter Source Type: research