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.