Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase

Karen E. Chaffin, Chan R. Beals, Thomas M. Wilkie, Katherine A. Forbush, Melvin I. Simon, Roger M. Perlmutter

Research output: Contribution to journalArticlepeer-review

223 Scopus citations


Stimulation of the T lymphocyte antigen receptor-CD3 complex (TCR-CD3) causes T cell activation by a process associated with increased phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Evidence exists suggesting that GTP-binding (G) proteins, particularly the pertussis toxin (PT)-sensitive Gi proteins, participate in this signal transduction pathway. To clarify the role of Gi proteins in TCR-CD3 signaling, and to investigate other possible functions of Gi molecules in T cells, we expressed the S1 subunit of PT in the thymocytes of transgenic mice using the lymphocyte-specific lck promoter. Transgenic thymocytes contained S1 activity and exhibited profound depletion of Gi protein PT substrates in a manner suggesting their inactivation by S1 in vivo. Nevertheless, treatment of transgenic thymocytes with mitogenic stimuli provoked normal increases in intracellular free Ca2+ concentrations and IL-2 secretion, indicating that Gi proteins are not required for T cell activation. These normal signaling responses notwithstanding, mature thymocytes accumulated in lck-PT mice and did not appear in secondary lymphoid organs or in the circulation. Viewed in the context of the known features of Bordetella pertussis infection, our results suggest that a PT-sensitive signaling process, probably involving Gi proteins, regulates thymocyte emigration.

Original languageEnglish (US)
Pages (from-to)3821-3829
Number of pages9
JournalEMBO Journal
Issue number12
StatePublished - 1990


  • G protein
  • Pertussis toxin
  • Signal transduction
  • T cell antigen receptor
  • T lymphocyte

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Molecular Biology
  • General Neuroscience


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