Overexpression of Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomains induces cluster of differentiation 59-mediated apoptosis in Jurkat cells

Abstract

Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomains (CBP/PAG) is a membrane-bound adaptor protein that downregulates the activation of Src family kinases present in lipid rafts. To elucidate the role of CBP/PAG in human T cell activation, a cell line overexpressing CBP/PAG was constructed and the function of CBP/PAG in Jurkat cells was examined. The present study revealed that increased CBP/PAG expression in T cells significantly enhanced their apoptosis and reduced cellular activation and proliferation. Overexpression of CBP/PAG suppressed the growth of Jurkat cells by recruiting c-Src and its negative regulator, C-terminal Src kinase (CSK), to lipid rafts. The negative regulation of CBP/PAG was enhanced in the presence of anti-cluster of differentiation (CD)59 monoclonal antibodies. In addition, a significant association was revealed between the location of CBP/PAG and CD59, which were co-expressed in the same region of the cell membrane, implicating a potential overlap of the elicited signaling pathways. These results indicate that CBP/PAG functions as a negative regulator of cell signal transduction and suggest that CD59 may strengthen the role of negative feedback regulation.

Regulation, targets and functions of CSK

“…By recruiting CSK to lipid rafts where Src is enriched, CBP reduces T cell growth/ proliferation and enhances T cell apoptosis. Meanwhile, CBP is synergistically strengthened by CD59 (Cong et al, 2018). The detailed molecular mechanism in CSK-mediated T cell apoptosis is described in detail by Fortner et al, 2022. T cell effector function depends on TNF receptor associated factor 3 (TRAF3).…”