Understanding signal integration through targeted mutations of an adapter protein

Immunoreceptor engagement leads to the activation of multiple second messenger cascades, and integration of these pathways requires proper function of a number of adapter proteins. Although adapters possess no intrinsic enzymatic function, they nucleate the formation of multi-molecular protein complexes to support downstream signaling. Since adapters contain functionally distinct domains, intense investigation has been devoted to understanding how these regions act to integrate signals. This review describes the evolution of studies investigating one of these adapters, the SH2 domain-containing leukocyte protein of 76 kDa. Through utilizing biochemical, genetic and imaging techniques, a model has emerged describing how this adapter regulates signals resulting in complex immune responses.