Lars Henrik Fugger

Constitutively active Lck kinase in T cells drives antigen receptor signal transduction

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Konstantina Nika, Denmark
  • Cristiana Soldani, Denmark
  • Mogjiborahman Salek, Denmark
  • Wolfgang Paster, Denmark
  • Adrian Gray, Denmark
  • Ruth Etzensperger, Denmark
  • Lars Fugger
  • Paolo Polzella, Denmark
  • Vincenzo Cerundolo, Denmark
  • Omer Dushek, Denmark
  • Thomas Höfer, Denmark
  • Antonella Viola, Denmark
  • Oreste Acuto, Denmark
  • The Department of Clinical Immunology
T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was readily detectable in these cells in lymphoid organs. In naive T cells up to approximately 40% of total Lck was constitutively activated, part of which was also phosphorylated on the C-terminal inhibitory site. Formation of activated Lck was independent of TCR and coreceptors but required Lck catalytic activity and its maintenance relied on monitoring by the HSP90-CDC37 chaperone complex to avoid degradation. The amount of activated Lck did not change after TCR and coreceptor engagement; however it determined the extent of TCR-zeta phosphorylation. Our findings suggest a dynamic regulation of Lck activity that can be promptly utilized to initiate T cell activation and have implications for signaling by other immune receptors.
Original languageEnglish
Pages (from-to)766-77
Number of pages11
Publication statusPublished - 2010

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