Immunoreceptor tyrosine-based inhibitory motif

Chacko el al., 1996). Cell growth is arrested when the type II Fey receptor bl (FcyRIIbl) associates with the B cell receptor (BCR) by the interaction of their extracellular domains with immune complexes. Clustering FcyRIIbl with BCR induces the phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) within the FcyRIIb intracellular tail, which then allows SHIP to bind through its SH2 domain. Recruitment of SHIP to the cell membrane by FcyRIIb p-ITIM is believed to block extracellular Ca2+ uptake and cell growth via the inositol 5-phosphatase activity of SHIP. 

SHIP SH2 domain binds to the phosphorylated H IM (p-ITIM) of other inhibitory co-receptors (gp49Bl) (Kuroiwa etal., 1998) and to the p-ITIM-like motif of the adhesion receptor, PECAM-1 (Pumphrey et al., 1999), furthermore, in vitro it binds to the phosphorylated immunoreceptor tyrosine based activation motifs (p-ITAM) within the p and y subunits of the high affinity IgE receptor (Kimura et al. 1997)), and the zeta chain of T cell receptor (Osborne et al., 1996). However, in vivo coprecipitation of these molecules was not observed. 

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