An early event in T cell antigen receptor (TCR)-mediated signal transduction is the activation of a protein tyrosine kinase (PTK) pathway. An unidentified PTK activity and a kinase substrate termed ZAP-70 have previously been shown to associate with TCRζ upon cross-linking of TCRβ. Here we report that TCR activation, by antibody cross-linking of either TCRβ or CD3∈, results in the association of a PTK activity with both CD3 and TCRζ. A number of in vitro PTK substrates are also associated with CD3 and TCRζ, including CD3∈, TCRζ, p60fyn, p62yes, and a predominant 70-kDa protein (ZAP-70). The shared PTK activity and PTK substrates suggest that both CD3 and TCRζ are involved in signal transduction via a shared pathway. We used [α-32P]γ-azidoanilido ATP, a photoreactive analogue of ATP, to detect CD3-associated proteins that bound ATP upon TCR activation, reasoning that such proteins could represent PTKs. A 70-kDa protein bound [α-32P]γ-azidoanilido ATP only upon TCR activation, and we propose that this protein and the 70-kDa PTK substrate are the same protein. Furthermore, we propose that this protein is responsible for the PTK activity observed to be associated with TCRζ and CD3 upon TCR activation.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - Jun 15 1992|
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