Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 19 April 2011
Vol. 4, Issue 169, p. ra24
[DOI: 10.1126/scisignal.2001309]

RESEARCH ARTICLES

Editor's Summary

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 Fc{varepsilon}RI resulted in its colocalization with FcαRI and SHP-1 in rafts, and the assembled proteins were internalized into intracellular structures called "inhibisomes," which prevented Fc{varepsilon}RI 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).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Specific inactivation of two immunomodulatory SIGLEC genes during human evolution.
X. Wang, N. Mitra, I. Secundino, K. Banda, P. Cruz, V. Padler-Karavani, A. Verhagen, C. Reid, M. Lari, E. Rizzi, et al. (2012)
PNAS 109, 9935-9940
   Abstract »    Full Text »    PDF »
ITAM-Coupled Receptors Inhibit IFNAR Signaling and Alter Macrophage Responses to TLR4 and Listeria monocytogenes.
L. Huynh, L. Wang, C. Shi, K.-H. Park-Min, and L. B. Ivashkiv (2012)
J. Immunol. 188, 3447-3457
   Abstract »    Full Text »    PDF »
IgG1 and IVIg induce inhibitory ITAM signaling through Fc{gamma}RIII controlling inflammatory responses.
M. Aloulou, S. Ben Mkaddem, M. Biarnes-Pelicot, T. Boussetta, H. Souchet, E. Rossato, M. Benhamou, B. Crestani, Z. Zhu, U. Blank, et al. (2012)
Blood 119, 3084-3096
   Abstract »    Full Text »    PDF »
How ITAMs Inhibit Signaling.
L. B. Ivashkiv (2011)
Science Signaling 4, pe20
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882