Microglial Immunoreceptor Tyrosine-Based Activation and Inhibition Motif Signaling in Neuroinflammation

Figure 1

ITAM-/ITIM-signaling cascade. Left side: Upon ligand binding, activatory receptors like TREM2, SIRP𝛽1, Fc𝛾RI or FcγRIIIA associate with ITAM containing adaptor proteins such as DAP12 or the common 𝛾 chains through interactions between charged amino acids (−/+) within the transmembrane regions of each protein. Subsequently, members of Src kinase family (SKF) phosphorylate tyrosine residues of ITAMs. Phosphotyrosine residues are docking sites for Syk protein kinases that upon activation mediate cellular activation via a number of downstream cascades. Right side: Upon ligand binding, inhibitory receptors like most Siglecs recruit SHP1 and SHP2 which can in turn terminate intracellular signals emanating from ITAM receptors.