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 language | English (US) |
|---|---|
| Pages (from-to) | 3821-3829 |
| Number of pages | 9 |
| Journal | EMBO Journal |
| Volume | 9 |
| Issue number | 12 |
| State | Published - 1990 |
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Keywords
- G protein
- Pertussis toxin
- Signal transduction
- T cell antigen receptor
- T lymphocyte
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase
AU - Chaffin, Karen E.
AU - Beals, Chan R.
AU - Wilkie, Thomas M.
AU - Forbush, Katherine A.
AU - Simon, Melvin I.
AU - Perlmutter, Roger M.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - G protein
KW - Pertussis toxin
KW - Signal transduction
KW - T cell antigen receptor
KW - T lymphocyte
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UR - http://www.scopus.com/inward/citedby.url?scp=0025119207&partnerID=8YFLogxK
M3 - Article
C2 - 2123451
AN - SCOPUS:0025119207
VL - 9
SP - 3821
EP - 3829
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 12
ER -