A novel ZAP-70 dependent FRET based biosensor reveals kinase activity at both the immunological synapse and the antisynapse

PLoS One. 2008 Jan 30;3(1):e1521. doi: 10.1371/journal.pone.0001521.

Abstract

Many hypotheses attempting to explain the speed and sensitivity with which a T-cell discriminates the antigens it encounters include a notion of relative spatial and temporal control of particular biochemical steps involved in the process. An essential step in T-cell receptor (TCR) mediated signalling is the activation of the protein tyrosine kinase ZAP-70. ZAP-70 is recruited to the TCR upon receptor engagement and, once activated, is responsible for the phosphorylation of the protein adaptor, Linker for Activation of T-cells, or LAT. LAT phosphorylation results in the recruitment of a signalosome including PLCgamma1, Grb2/SOS, GADS and SLP-76. In order to examine the real time spatial and temporal evolution of ZAP-70 activity following TCR engagement in the immune synapse, we have developed ROZA, a novel FRET-based biosensor whose function is dependent upon ZAP-70 activity. This new probe not only provides a measurement of the kinetics of ZAP-70 activity, but also reveals the subcellular localization of the activity as well. Unexpectedly, ZAP-70 dependent FRET was observed not only at the T-cell -APC interface, but also at the opposite pole of the cell or "antisynapse".

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques*
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Subcellular Fractions / metabolism
  • Synapses / immunology
  • Synapses / metabolism*
  • T-Lymphocytes / immunology
  • ZAP-70 Protein-Tyrosine Kinase / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / physiology*

Substances

  • Protein Kinases
  • ZAP-70 Protein-Tyrosine Kinase