The T-cell receptor (TCR) ζ subunit is an important component of the TCR complex, involved in signal transduction events following TCR engagement. In this study, we showed that the TCR ζ chain is constitutively tyrosine phosphorylated to similar extents in thymocytes and lymph node T cells. Approximately 35% of the tyrosine-phosphorylated TCR ζ (phospho ζ) precipitated from total cell lysates appeared to be surface associated. Furthermore, constitutive phosphorylation of TCR ζ in T cells occurred independently of antigen stimulation and did not require CD4 or CD8 coreceptor expression. In lymph node T cells that constitutively express tyrosine-phosphorylated TCR ζ, there was a direct correlation between surface TCR-associated protein tyrosine kinase (PTK) activity and expression of phospho ζ. TCR stimulation of these cells resulted in an increase in PTK activity that coprecipitated with the surface TCR complex and a corresponding increase in the levels of phospho ζ. TCR ligations also contributed to the detection of several additional phosphoproteins that coprecipitated with surface TCR complexes, including a 72-kDa tyrosine-phosphorylated protein. The presence of TCR-associated PTK activity also correlated with the binding of a 72-kDa protein, which became tyrosine phosphorylated in vitro kinase assays, to tyrosine phosphorylated TCR ζ. The cytoplasmic region of the TCR ζ chain was synthesized, tyrosine phosphorylated, and conjugated to Sepharose beads. Only tyrosine-phosphorylated, not nonphosphorylated, TCR ζ beads were capable of immunoprecipitating the 72-kDa protein from total cell lysates. This 72-kDa protein is likely the murine equivalent of human PTK ZAP-70, which has been shown to associate specifically with phospho ζ. These results suggest that TCR-associated PTK activity is regulated, at least in part, by the tyrosine phosphorylation status of TCR ζ.
|Original language||English (US)|
|Number of pages||10|
|Journal||Molecular and cellular biology|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology