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 journalArticle

212 Citations (Scopus)

Abstract

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
Volume9
Issue number12
StatePublished - 1990

Fingerprint

ADP Ribose Transferases
Dissection
Pertussis Toxin
Thymocytes
T-cells
T-Cell Antigen Receptor-CD3 Complex
T-Lymphocytes
Proteins
GTP-Binding Proteins
Bordetella Infections
Chemical activation
Phosphoinositide Phospholipase C
Bordetella pertussis
Signal transduction
Antigen Receptors
Lymphocytes
Viral Tumor Antigens
Emigration and Immigration
Guanosine Triphosphate
Transgenic Mice

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Chaffin, K. E., Beals, C. R., Wilkie, T. M., Forbush, K. A., Simon, M. I., & Perlmutter, R. M. (1990). Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. EMBO Journal, 9(12), 3821-3829.

Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. / Chaffin, Karen E.; Beals, Chan R.; Wilkie, Thomas M.; Forbush, Katherine A.; Simon, Melvin I.; Perlmutter, Roger M.

In: EMBO Journal, Vol. 9, No. 12, 1990, p. 3821-3829.

Research output: Contribution to journalArticle

Chaffin, KE, Beals, CR, Wilkie, TM, Forbush, KA, Simon, MI & Perlmutter, RM 1990, 'Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase', EMBO Journal, vol. 9, no. 12, pp. 3821-3829.
Chaffin, Karen E. ; Beals, Chan R. ; Wilkie, Thomas M. ; Forbush, Katherine A. ; Simon, Melvin I. ; Perlmutter, Roger M. / Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. In: EMBO Journal. 1990 ; Vol. 9, No. 12. pp. 3821-3829.
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