- Signal transduction by the T cell and B cell antigen receptors and by receptors for a variety of immunoglobulins’ Fc region is strictly dependent on a receptor subunit cytoplasmic module termed immunoreceptor tyrosine-based activation motif (11AM). Thit module exists in one or more copies in each of the receptor-associated signal-transducing molecules and it possesses two repeats of the consensus sequence Tyr-X-X-Leuflle spaced by six to eight amino acids. Receptor engagement is followed by a rapid and transient phosphorylation oftyrosine residues within their ITAMS, thereby creating temporary binding sites for Src homology 2 (SH2)-containing signaling molecules operating downstream of the activated receptor. The purpose of this review is to discuss recent findings on the functional role ofiTAMs in antigen and Fc receptormediated signal transduction, with a particular emphasis on kinases operating upstream and downstream of the ITAMs. J. Leukoc. Biol. 61: 6-16; 1997.