Inhibitory receptors, ITIM sequences and phosphatases

A diverse group of inhibitory receptors, including Fc gamma RII, killer cell inhibitory receptors, and B22, shares an immunoreceptor tyrosine-based inhibition motif (ITIM). Recent studies have shown that this motif, when phosphorylated on tyrosine, forms a docking site for the Src homology 2 recognition domains of the protein tyrosine phosphatase SHP-1 and the inositol 5-phosphatase SHIP. A similar motif in cytotoxic T-lymphocyte antigen-4 recruits the related tyrosine phosphatase SHP-2. These three enzymes act to inhibit signaling cascades resulting from ligation of the BCR, TCR, Fc gamma RIII, and Fc epsilon RI, although the relative importance of the tyrosine phosphatases and the inositol phosphatase differs depending on the cell type.