Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

Figure 4

CD200R-induced signaling pathway. Interaction of CD200R with its ligand induces phosphorylation of the tyrosine residues (red squares) present in the intracellular portion of the receptor mediated by kinases of the Src family. This mechanism propitiates recruitment of Dok2 through its binding domain to tyrosine (PTB). Dok2 binds to the phosphorylated tyrosines, and it recruits the activator protein of Ras-GTPase (RasGAP), which inhibits Ras and downstream ERK activation. ERK is a MAP kinase which is involved in macrophages activation by IFN-γ. JAK/STAT-1 signaling pathway is required for cell activation, and STAT-1 is phosphorylated by JAK proteins and ERK-1/2 in turn to allow the gene expression for cell differentiation, growth and metabolism, so then, if CD200R binds to its ligand CD200 it allows the inhibition of cell activation [74, 95].