Research ArticleImmunology

Dimerization of the adaptor Gads facilitates antigen receptor signaling by promoting the cooperative binding of Gads to the adaptor LAT

See allHide authors and affiliations

Sci. Signal.  26 Sep 2017:
Vol. 10, Issue 498, eaal1482
DOI: 10.1126/scisignal.aal1482

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Gads’ commitment to signaling

Binding of antigen to cell surface receptors on immune cells stimulates the formation of multiprotein complexes (signalosomes) that center around adaptor proteins, such as LAT, and are mediated by the interactions of Src homology 2 (SH2) domain–containing proteins with phosphotyrosine residues in LAT. Despite having only one SH2 domain, the adaptor protein Gads preferentially binds to LAT molecules that have more than one phosphotyrosine. Through biochemical studies and mathematical modeling, Sukenik et al. showed that constitutive dimerization of Gads through its SH2 domain enabled this adaptor to discriminate between singly and multiply phosphorylated LAT proteins. Disruption of the Gads dimerization interface impaired antigen receptor signaling in T cells and mast cells. These data suggest that through dimerization, Gads commits to forming signalosomes around fully phosphorylated LAT molecules, thus promoting antigen receptor responsiveness.