Immunoreceptor tyrosine activation motifs domains

Finally, platelets can be activated by immune complexes following binding of immunoglobulin G (IgG) Fc domains to platelet Fey RII. This process involves tyrosine phosphorylation of a motif designated as ITAM (immunoreceptor tyrosine-based motif) found on the cytoplasmic domain of platelet Fey RII receptors (73). This may play a role in immune complex diseases, particularly in heparin-induced thrombocytopenia. 

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. 

Ig-a-Ig-P heterodimers. The intracellular domains of each of the Ig-a and Ig-[3 chains include an immunoreceptor tyrosine-based activation motif (ITAM). 

The protein p56 lymphoid T-cell tyrosine kinase (Lck) is predominantly expressed in T lymphocytes where it plays a critical role in T-cell-mediated immune response. Lck participates in phosphotyrosine-dependent protein-protein interactions through its modular binding unit, the Src homology-2 (SH2) domain. SH2 domains are noncatalytic modules of about 100 amino acid residues that play important roles in intracellular signal transduction and represent potential targets for pharmacological intervention. Failure of the p5 6 Lck S H 2 domain to bind to immunoreceptor tyrosine-based activation motifs (ITAMs) of CD3 hampers the T-cell receptor (TCR) proximal activation process and suppresses the downstream T-cell activation signaling cascades [143]. Small compounds that would be able to block Lck SH2 domain-dependent protein-protein interactions could find therapeutic utility as immunosuppressants and in the treatment of T-cell leukemias, lymphomas, and autoimmune diseases such as rheumatoid arthritis. 

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