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Sci. Signal., 19 April 2011
Vol. 4, Issue 169, p. ra24
Inhibition by Diversion
Signaling by receptors containing activating motifs called ITAMs stimulates pathways that lead to cellular activation. Paradoxically, ITAM receptors, including the immunoglobulin receptor FcαRI, can also inhibit signaling. Pfirsch-Maisonnas et al. found that the binding of low-affinity ligand resulted in the recruitment of FcαRI and the phosphatase SHP-1 to membrane lipid rafts. In a second step, ligation of the activating receptor FcRI resulted in its colocalization with FcαRI and SHP-1 in rafts, and the assembled proteins were internalized into intracellular structures called "inhibisomes," which prevented FcRI from activating its effectors. FcαRI also inhibited signaling by non–ITAM-containing receptors, which suggests that the recruitment of inhibitory ITAM receptors and SHP-1 to lipid rafts may constitute a general mechanism for the inhibition of activating receptors.
Citation: S. Pfirsch-Maisonnas, M. Aloulou, T. Xu, J. Claver, Y. Kanamaru, M. Tiwari, P. Launay, R. C. Monteiro, U. Blank, Inhibitory ITAM Signaling Traps Activating Receptors with the Phosphatase SHP-1 to Form Polarized "Inhibisome" Clusters. Sci. Signal.4, ra24 (2011).
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