Visperas1pY – Other Categories

An immuno-receptor tyrosine-based activation motif (ITAM) is a phosphorylation site consisting of a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of cell-surface non-catalytic tyrosine-phosphorylated receptors. ITAMs are involved activation of immune cells. The motif has the following structure: YxxL/I. where xx are any two amino acids. Two of these motifs are typically separated by between 6 and 8 amino acids in the cytoplasmic tail of the molecule (YxxL/Ix(6-8)YxxL/I). ITAMs are found in the CD3 and θ¶-chains of the T cell receptor (TCR) complex. TCR is a multi-subunit receptor on the surface of T cells which contains two ligand binding chains containing 20 phosphorylation sites, distributed on 10 ITAMs. The TCR θ¶-chain is a homodimer subunit that contains six ITAMs (12 sites). These sites are phosphorylated by the membrane-anchored Src family tyrosine kinase Lck and Fyn and are dephosphorylated by the transmembrane phosphatases CD148 and CD45. When both tyrosines in an ITAM are phosphorylated they generate docking sites for the tandem SH2 domains of the cytosolic tyrosine kinase ZAP-70. Bound ZAP-70 can phosphorylate tyrosines on other substrates that initiate the signal transduction that leads to T cell activation. The multiple ITAMs on the TCR function mainly to amplify subsequent signalling. T cells rely on the TCR to recognize antigens, in the form of peptides bound to major histocompatibility complexes (MHC), on the surfaces of antigen-presenting cells. Binding of TCR to antigen-MCH complexes leads to proliferation, differentiation, and the secretion of effector cytokines, contributing to the elimination of infections.