• mast cells;
  • immunoreceptor tyrosine-based activation motif;
  • immunoreceptor tyrosine-based inhibitory motif;
  • inflammatory response;
  • cell signaling;
  • regulation

Summary:  The type I Fcε receptor (FcεRI) is one of the better understood members of its class and is central to the immunological activation of mast cells and basophils, the key players in immunoglobulin E (IgE)-dependent immediate hypersensitivity. This review provides background information on several distinct regulatory mechanisms controlling this receptor’s stimulus–response coupling network. First, we review the current understanding of this network’s operation, and then we focus on the inhibitory regulatory mechanisms. In particular, we discuss the different known cytosolic molecules (e.g. kinases, phosphatases, and adapters) as well as cell membrane proteins involved in negatively regulating the FcεRI-induced secretory responses. Knowledge of this field is developing at a fast rate, as new proteins endowed with regulatory functions are still being discovered. Our understanding of the complex networks by which these proteins exert regulation is limited. Although the scope of this review does not include addressing several important biochemical and biophysical aspects of the regulatory mechanisms, it does provide general insights into a central field in immunology.