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ITIM/ITAM Immunoreceptors and Related Molecules

ITIMs (immunoreceptor tyrosine-based inhibition motif; S/I/V/LxYxxI/V/L) and ITAMs (immunoreceptor tyrosine-based activation motif; consensus sequence YxxI/Lx6-12YxxI/L) are phosphorylation motifs found in a large number of receptors or adaptor proteins. Phosphorylated ITAMs serve as docking sites for tandem SH2 domains of Syk family kinases, whereas phosphorylated ITIMs recruit tyrosine phosphatases. Signaling through ITAM-bearing receptors usually results in cell activation, while engagement of ITIM-bearing receptors is usually inhibitory, although exceptions have been described. The majority of these receptors are involved in tumor development and regulation of the immune system, although some also function in tissues such as bone and brain.