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Sci. Signal., 13 September 2011
Vol. 4, Issue 190, p. ra59
[DOI: 10.1126/scisignal.2001893]

RESEARCH ARTICLES

Editor's Summary

Poised for Activation
The activity of the Src family kinase Lck is blocked by the phosphorylation of an inhibitory tyrosine residue by the cytoplasmic C-terminal Src kinase, Csk. In response to engagement of the T cell receptor (TCR) by agonist peptide, Csk is lost from the plasma membrane, and dephosphorylation of the inhibitory residue by the phosphatase CD45 enables Lck to activate signaling downstream of the TCR. In experiments in T cells containing a membrane-anchored, analog-sensitive mutant of Csk, Schoenborn et al. found that inhibition of Csk was sufficient to induce activation of Lck independently of ligand binding to the TCR and that the resulting signaling was enhanced and prolonged compared to that in TCR-stimulated cells. Together, these findings demonstrate ligand-independent, basal TCR signaling, which suggests that molecules downstream of the TCR are poised to respond to receptor activation but are restrained by the inhibitory kinase Csk.

Citation: J. R. Schoenborn, Y. X. Tan, C. Zhang, K. M. Shokat, A. Weiss, Feedback Circuits Monitor and Adjust Basal Lck-Dependent Events in T Cell Receptor Signaling. Sci. Signal. 4, ra59 (2011).

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