Research ArticleImmunology

Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling

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Science Signaling  26 Jul 2016:
Vol. 9, Issue 438, pp. ra75
DOI: 10.1126/scisignal.aaf0626

Releasing the membrane to signal

In addition to signaling by the T cell receptor (TCR), signaling by the costimulatory receptor CD28 is required for full activation of naïve T cells and the generation of regulatory T (Treg) cells. Dobbins et al. used fluorescence-based techniques to show that positively charged (basic) amino acids in the cytoplasmic domain of CD28 mediated its interaction with the negatively charged inner leaflet of the plasma membrane. Ligand binding to CD28 triggered the release of the cytoplasmic domain, thus making the basic residues available for binding to the effector kinase Lck and recruiting downstream components of the signaling pathway. Mice with T cells expressing a mutant CD28 devoid of its C-terminal basic amino acids were defective in Treg cell generation. These basic regions of CD28 have dual function, maintaining inactivity by membrane interaction and promoting activity by binding to Lck.

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