Conformational states of the kinase Lck regulate clustering in early T cell signaling

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2013
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Owen, Dylan M.
Williamson, David J.
Yang, Zhengmin
Gaus, Katharina
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Nature Immunology. 2013, 14(1), pp. 82-89. ISSN 1529-2908. eISSN 1529-2916. Available under: doi: 10.1038/ni.2488
Zusammenfassung

Phosphorylation of the T cell antigen receptor (TCR) by the tyrosine kinase Lck is an essential step in the activation of T cells. Because Lck is constitutively active, spatial organization may regulate TCR signaling. Here we found that Lck distributions on the molecular level were controlled by the conformational states of Lck, with the open, active conformation inducing clustering and the closed, inactive conformation preventing clustering. In contrast, association with lipid domains and protein networks were not sufficient or necessary for Lck clustering. Conformation-driven Lck clustering was highly dynamic, so that TCR triggering resulted in Lck clusters that contained phosphorylated TCRs but excluded the phosphatase CD45. Our data suggest that Lck conformational states represent an intrinsic mechanism for the intermolecular organization of early T cell signaling.

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570 Biowissenschaften, Biologie
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ISO 690ROSSY, Jérémie, Dylan M. OWEN, David J. WILLIAMSON, Zhengmin YANG, Katharina GAUS, 2013. Conformational states of the kinase Lck regulate clustering in early T cell signaling. In: Nature Immunology. 2013, 14(1), pp. 82-89. ISSN 1529-2908. eISSN 1529-2916. Available under: doi: 10.1038/ni.2488
BibTex
@article{Rossy2013-01Confo-43329,
  year={2013},
  doi={10.1038/ni.2488},
  title={Conformational states of the kinase Lck regulate clustering in early T cell signaling},
  number={1},
  volume={14},
  issn={1529-2908},
  journal={Nature Immunology},
  pages={82--89},
  author={Rossy, Jérémie and Owen, Dylan M. and Williamson, David J. and Yang, Zhengmin and Gaus, Katharina}
}
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