Coupling of GTP-binding to the T cell receptor (TCR) ζ-chain with TCR- mediated signal transduction

Jaime Sancho, Marcus E. Peter, Rafael Franco, Silvia Danielian, Jae Seung Kang, Remi Fagard, Jamilé Woods, John C. Reed, Malek Kamoun, Cox Terhorst

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The ζ-subunit of the TCR binds GTP and is a well characterized substrate for a TCR-activated tyrosine kinase. To examine the possible coupling of GTP- binding to ζ with TCR-mediated signal transduction, a mutant (termed J32- 3.2) of the T cell line Jurkat (J32) was used. Anti-TCR/CD3 stimulation of the TCR/CD3+ J32-3.2 cells resulted in a weak stimulation of both the phosphatidyl inositol and tyrosine kinase signal transduction pathways, as measured by changes in the level of free intracellular calcium, tyrosine phosphorylation of TCR-ζ, CD3-ε and ZAP-70, p56(lck), or p59(fyn) tyrosine kinase activity and IL-2 gene activation. The impaired responsiveness of J32- 3.2 cells to anti-TCR/CD3 mAb correlated with a low basal level of GTP- binding to ζ. Furthermore, in J32-3.2 cells TCR activation by antibody ligation caused a weaker increase in GTP-binding to the ζ-chain, as compared with that of wild-type J32 cells, which indicates for the first time that GTP-binding to ζ can be modulated by extracellular signals and suggest that the role of GTP-binding to ζ is to couple the TCR to intracellular signal transduction mechanisms.

Original languageEnglish (US)
Pages (from-to)3230-3242
Number of pages13
JournalJournal of Immunology
Volume150
Issue number8 I
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sancho, J., Peter, M. E., Franco, R., Danielian, S., Kang, J. S., Fagard, R., Woods, J., Reed, J. C., Kamoun, M., & Terhorst, C. (1993). Coupling of GTP-binding to the T cell receptor (TCR) ζ-chain with TCR- mediated signal transduction. Journal of Immunology, 150(8 I), 3230-3242.