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 language||English (US)|
|Number of pages||13|
|Journal||Journal of Immunology|
|Issue number||8 I|
|State||Published - 1993|
ASJC Scopus subject areas
- Immunology and Allergy