How do multichain immune recognition receptors signal? A structural hypothesis

Several cell surface receptors involved in cellular activation by antigen, such as the B-cell and T-cell antigen receptors, and receptors for IgE and IgG (Fc epsilon RI and Fc gamma RIII) show substantial similarities in structure and signaling pathways. An essential step in the activation of immune cells through these receptors is the phosphorylation of specific tyrosine residues within certain consensus sequences found in the cytoplasmic tails of different chains belonging to each of these receptors. The mechanism by which aggregation of the receptors triggers these phosphorylation is still unknown. In this paper, a mechanistic model for this key event is proposed. This model assumes that the kinase(s) responsible for catalysing these phosphorylations do exist associated with the receptors, but for steric reasons they cannot phosphorylate tyrosine residues on chains of the same receptor complex. Upon aggregation, these kinases phosphorylate the tyrosines of a distinct receptor complex (cross-phosphorylation), thus starting the signaling cascade.