High resolution

Module 2: Figure ROS effects on Ca2+ signalling



Reciprocal interaction between the ROS and Ca2+ signalling pathways during B cell receptor (BCR) activation.

Cross-linking the B cell receptor (BCR) with antigen sets up a protein phosphorylation cascade that begins with Lyn phosphorylating both the receptor and Syk. The latter then binds to the phosphorylated receptor, where it phosphorylates the adaptor protein B cell linker (BLNK) and the tyrosine kinase Bruton's tyrosine kinase (Btk). The latter phosphorylates BLNK and phospholipase Cγ2 (PLCγ2), which associates with BLNK and begins to hydrolyse PtdIns4,5P2 to form inositol 1,4,5-trisphosphate (IP3). This phosphorylation cascade is kept in check by the tyrosine phosphatase Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1 (SHP-1). One of the functions of the Ca2+ released by IP3 is to set up a positive-feedback loop based on the activation of the Ca2+-sensitive enzyme dual oxidase (DUOX) that generates hydrogen peroxide (H2O2). The latter feeds back to inhibit SHP-1, which enables the signalling cascade to work more effectively in generating Ca2+ signals. This formation of H2O2 is highly localized as a microdomain in the immediate vicinity of the BCR (Module 2: Figure ROS microdomains). This figure is based on information taken from Singh et al. 2005.