Article Dans Une Revue Cellular Signalling Année : 2020

The adaptor protein APS modulates BCR signalling in mature B cells

Résumé

Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways, switched on and off all through late B cell differentiation stages. Mice deficient for APS, a member of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role in mature B cells. However, the intermediates involved in this adaptor modulating functions in B cells are still unknown. In the present study, we investigated the role of APS in regulating BCR signalling notably through cytoskeleton remodeling in mature B cells. Herein, we showed that APS function is stage specific, as it exclusively intervenes in mature B cells. Upon activation, APS colocalizes with the BCR and associates with important regulators of BCR signalling, such as Syk and Cbl kinase. Importantly, APS interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is mainly mediated by APS SH2 domain, which regulates BCR-evoked cell dynamics. Our findings thus reveal that APS plays a regulatory role in BCR-induced responses by specifically modulating its interacting partners, which positions APS as a relevant modulator of BCR signalling in mature B cells.

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hal-03085795 , version 1 (22-12-2020)

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Elisabetta Dondi, Jean-Baptiste Sibarita, Nadine Varin-Blank, Laura Velazquez. The adaptor protein APS modulates BCR signalling in mature B cells. Cellular Signalling, 2020, 73, ⟨10.1016/j.cellsig.2020.109673⟩. ⟨hal-03085795⟩
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