Ac. Chan et al., DIFFERENTIAL EXPRESSION OF ZAP-70 AND SYK PROTEIN-TYROSINE KINASES, AND THE ROLE OF THIS FAMILY OF PROTEIN-TYROSINE KINASES IN TCR SIGNALING, The Journal of immunology, 152(10), 1994, pp. 4758-4766
TCR stimulation results in the tyrosine phosphorylation of a number of
cellular substrates. We have recently identified a 70-kDa protein tyr
osine kinase, ZAP-70, which associates with the human TCR zeta-chain a
fter TCR stimulation. We report here the isolation and sequence of a c
DNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93
% amino acid identity and are homologous to the 72-kDa protein tyrosin
e kinase Syk. Syk has been implicated in the signal transduction pathw
ays of the B cell membrane Ig and high affinity IgE receptors, Fc epsi
lon RI. In addition, we examined the tissue distribution of ZAP-70 and
Syk in human and murine thymocyte subsets, B cells, and peripheral T
cell subsets. ZAP-70 protein is expressed in all major thymocyte popul
ations, with the level of expression being comparable to that found in
both CD4(+) and CD8(+) peripheral T cells. Although Syk protein is al
so present in all thymocyte subsets, expression of Syk protein is down
-regulated threefold to fourfold in peripheral T cells. In contrast to
ZAP-70, expression of Syk is 12- to 15-fold higher in peripheral B ce
lls when compared with peripheral T cells. In addition, whereas T cell
stimulation results in down-regulation of Lck, no significant change
in ZAP-70 or Syk protein is detected. Finally, we provide evidence tha
t both ZAP-70 and Syk can associate with the TCR after TCR stimulation
. With the use of a heterologous expression system, we show that, like
ZAP-70, Syk is dependent upon a Src-family protein tyrosine kinase fo
r association with the phosphorylated zeta-chain. Thus, the differenti
al expression of these kinases suggests the possibility of different r
oles for ZAP-70 and Syk in TCR signaling and thymic development.