Role of ITAM signaling module in signal integration

► ITAM-containing immunoreceptors couple with several classes of heterologous receptors to initiate context-specific cellular functions. ► The logic of coupling the ITAM-module with the heterologous receptors is currently unclear. ► Heterologous receptors that do not contain ITAM motifs may directly engage ITAM adapters in their signaling pathway. ► Alternatively, they may indirectly access ITAM-supported functions by coupling to a relevant immunoreceptor. ► New concepts postulate how heterologous receptors collaborate to create unique signals by using a limited set of conserved signaling module.