Decoding the Language of Phosphorylation Site Dynamics

Immune defenses depend on the ability of immunoreceptors to recognize foreign antigens and initiate intracellular signaling when a pathogen is detected. Signal initiation requires spatial reorganization of proteins and site-specifi c receptor phosphorylation, which leads to engagement of feedback loops. This Journal Club discusses recent work using combined experimental and computational approaches to investigate these processes in B cell antigen receptor (BCR) signaling. Specifically, the roles of different kinases in the presence and absence of BCR clustering were evaluated. Results indicated that spleen tyrosine kinase (SYK) can compensate for loss of Src-family kinase activity when receptors are spatially clustered, in part because receptor clustering enables SYK to trigger a positive feedback loop. This study and its implications suggest additional uses for computational models in studies of immunoreceptor signaling and highlight areas where extensions of current methodology are needed to better understand the complexities of biomolecular interactions.