Immunoreceptor tyrosine-based inhibitory motif

An immunoreceptor tyrosine-based inhibition motif (ITIM), is a conserved sequence of amino acids that is found in the cytoplasmic tails of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family found on immune cells. [1][2] It has the signature S/I/V/LxYxxI/V/L, where x stands for any amino acid, Y for a tyrosine residue that can be phosphorylated and S, I, V for amino acids serine, isoleucine, and valine, respectively. [1] After ITIM-possessing inhibitory receptors interact with their ligand, their ITIM motif becomes phosphorylated by enzymes of the Src kinase family, allowing them to recruit other enzymes such as the phosphotyrosine phosphatases SHP-1 and SHP-2, or the inositol-phosphatase called SHIP. These phosphatases decrease the activation of molecules involved in cell signaling.[3] A list of human candidate ITIM-containing proteins has been generated by proteome-wide scans.[4]

Similarly, an Immunoreceptor tyrosine-based activation motif (ITAM) that plays an integral part in the activation of immune cells was defined.

References

  1. Veillette, A; Latour, S; Davidson, D (2002). "Negative regulation of immunoreceptor signaling". Annual Review of Immunology. 20: 669–707. doi:10.1146/annurev.immunol.20.081501.130710. PMID 11861615.
  2. Dushek O, Goyette J, van der Merwe PA (November 2012). "Non-catalytic tyrosine- phosphorylated receptors". Immunological Reviews. 250 (1): 258–276. doi:10.1111/imr.12008. PMID 23046135.
  3. Barrow A, Trowsdale J (2006). "You say ITAM and I say ITIM, let's call the whole thing off: the ambiguity of immunoreceptor signaling". Eur J Immunol. 36 (7): 1646–53. doi:10.1002/eji.200636195. PMID 16783855.
  4. Staub E, Rosenthal A, Hinzmann B (2004). "Systematic identification of immunoreceptor tyrosine-based inhibitory motifs in the human proteome". Cell Signal. 16 (4): 435–456. doi:10.1016/j.cellsig.2003.08.013. PMID 14709333.


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