ITAMs: immunoregulatory scaffolds that link immunoreceptors to their intracellular signaling pathways.

Antigen receptors on the surface of T and B lymphocytes and various immunoglobulin Fc receptors are complexed multi-subunit structures that possess unique cytoplasmic modules, termed immunoreceptor tyrosine-based activation motif (ITAM). These modules consist of two repeats of the conserved sequence Tyr-X-X-Leu/lle spaced by six-to-eight residues and they function as 'on and off' switches that link the receptors to their intracellular signaling machinery. Thus, engagement of ITAM-containing receptors results in a rapid and transient phosphorylation of the ITAMs' tyrosine residues that function as temporal scaffolds for Src homology 2 (SH2) domains of downstream effector molecules. Recruitment and binding of these molecules to phospho-ITAMs initiate a cascade of biochemical events that lead to cell proliferation, differentiation, and acquisition of unique effector functions.