Motifs , immunoreceptors

In B lymphocytes, coupling of the antigen receptors to Erk MAPkinase is protein tyrosine kinase (PTK)-dependent (Pao et al, 1997). Following ligation of the BCR (Fig. 19.2) the PTK, Lyn, tyrosine phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) on the accessory transducing molecules Ig-a and Ig-(3, leading to the recruitment... 

ITAM Immunoreceptor tyrosine-based activation motif E(M) 0(0) 0(0) ... 

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. 

Osborne, M. A., Zenner, G., Lubinus, M., etal. (1996) The inositol 5 -phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation. J. Biol. Chem. 271,29,271-29,278. 

Nishimura, H., M. Nose, H. Hiai, N. Minato, and T. Honjo. 1999. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11 141-151. 

ITAM—immunoreceptor tyrosine-based activation 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. 

Lanier, L. L., Corliss, B. C., Wu, J., Leong, C., and Phillips, J. H. (1998b). Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Aatere 391 (6668), 703-707. 

Fig. 14.5 The TCR Complex is associated with a number of T< ll specific membrane-spanning proteins.31 The antigen receptors and the co-receptors, CDS, CD4, and CDS, together with associated enzymes, tyrosine kinases and phosphatases, form the actual signalling complex. The cytoplasmic chains of the co-receptor molecules have characteristic consensus sequences, the ITAMs (immunoreceptor tyrosine activation motife). Each of the invariant -chains and the CD3-y,8, e chains, contain 1-3 copies of the RAM motife. The structure of the TCR-signalling complex still needs to be clarified.

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). 

B. S. Gaul, M.L. Harrison, R.L. Geahlen, R.A. Burton, and C.B. Post. 2000. Substrate recognition by the Lyn protein-tyrosine kinase NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor Biol. Chem. 275 16174-16182. (PubMed)... 

---