Db. Straus et A. Weiss, THE CD3 CHAINS OF THE T-CELL ANTIGEN RECEPTOR ASSOCIATE WITH THE ZAP-70 TYROSINE KINASE AND ARE TYROSINE-PHOSPHORYLATED AFTER RECEPTOR STIMULATION, The Journal of experimental medicine, 178(5), 1993, pp. 1523-1530
Recent work indicates that signaling events resulting from stimulation
of the T cell antigen receptor (TCR) can be initiated by the CD3 comp
lex (gamma, delta, epsilon) as well as the zeta chains of the receptor
. To help characterize the signaling function of CD3 we examined its a
ssociated tyrosine kinase activity since induction of tyrosine phospho
rylation is one of the earliest signaling events. Our results indicate
that at least two kinases, lck and ZAP-70, contribute to the CD3-asso
ciated kinase activity. A likely target of this activity is the CD3 co
mplex itself since we observed that TCR stimulation resulted in rapid
tyrosine phosphorylation of the CD3epsilon and delta chains. To examin
e the function of the CD3epsilon chain in particular, we constructed a
chimera that fused the extracellular and transmembrane domains of CD8
to the cytoplasmic domain of CD3epsilon. This chimera demonstrated th
at CD3epsilon was independently capable of associating with proteins h
aving tyrosine kinase activity, including ZAP-70. Our results show tha
t the kinase activity that associates with the CD3 complex has charact
eristics that are quite similar to the previously characterized zeta-a
ssociated kinase activity. This finding suggests that both these compo
nents of the TCR initiate signaling events using a common mechanism. H
owever, differences in their signaling function could result from reco
gnition of distinct substrates.