Research ArticleImmunology

De novo phosphorylation and conformational opening of the tyrosine kinase Lck act in concert to initiate T cell receptor signaling

See allHide authors and affiliations

Sci. Signal.  17 Jan 2017:
Vol. 10, Issue 462, eaaf4736
DOI: 10.1126/scisignal.aaf4736

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

Lck: When an open conformation does not equal activation

The tyrosine kinase Lck is critical to T cell activation in response to stimulation of the T cell receptor (TCR). Lck activity is tightly regulated to avoid inappropriate activation of T cells and subsequent inflammation. Phosphorylation of Tyr505 causes Lck to form a closed, inhibited conformation, whereas phosphorylation of Tyr394 results in conformational opening of the kinase. To tease apart the differential effects of phosphorylation and conformational changes on Lck activity, Philipsen et al. generated different fluorescent Lck biosensors and imaged unstimulated and TCR-stimulated human T cells by fluorescence microscopy. Both the TCR-stimulated conformational opening of Lck and its subsequent phosphorylation of Tyr394 were required to stimulate T cells, and these modifications occurred primarily on Lck that was close to that TCR at the plasma membrane. These data suggest that drugs that stabilize the open conformation yet prevent the phosphorylation event could limit T cell–mediated immune responses.