Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling

Andrew C. Chan, Nicolai S C Van Oers A, Annie Tran, Larry Turka, Che Leung Law, James C. Ryan, Edward A. Clark, Arthur Weiss

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

TCR stimulation results in the tyrosine phosphorylation of a number of cellular substrates. We have recently identified a 70-kDa protein tyrosine kinase, ZAP-70, which associates with the human TCR ζ-chain after TCR stimulation. We report here the isolation and sequence of a cDNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93% amino acid identity and are homologous to the 72-kDa protein tyrosine kinase Syk. Syk has been implicated in the signal transduction pathways of the B cell membrane Ig and high affinity IgE receptors, FcεRI. 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 populations, with the level of expression being comparable to that found in both CD4+ and CD8+ peripheral T cells. Although Syk protein is also 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 cells 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 that 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 for association with the phosphorylated ζ-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development.

Original languageEnglish (US)
Pages (from-to)4758-4766
Number of pages9
JournalJournal of Immunology
Volume152
Issue number10
StatePublished - May 15 1994

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ZAP-70 Protein-Tyrosine Kinase
Protein-Tyrosine Kinases
Thymocytes
T-Lymphocytes
src-Family Kinases
B-Lymphocytes
B-Lymphocyte Subsets
IgE Receptors
Proteins
T-Lymphocyte Subsets
Tissue Distribution
Tyrosine
Signal Transduction
Phosphotransferases
Down-Regulation
Complementary DNA
Clone Cells
Phosphorylation
Cell Membrane
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. / Chan, Andrew C.; Van Oers A, Nicolai S C; Tran, Annie; Turka, Larry; Law, Che Leung; Ryan, James C.; Clark, Edward A.; Weiss, Arthur.

In: Journal of Immunology, Vol. 152, No. 10, 15.05.1994, p. 4758-4766.

Research output: Contribution to journalArticle

Chan, Andrew C. ; Van Oers A, Nicolai S C ; Tran, Annie ; Turka, Larry ; Law, Che Leung ; Ryan, James C. ; Clark, Edward A. ; Weiss, Arthur. / Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. In: Journal of Immunology. 1994 ; Vol. 152, No. 10. pp. 4758-4766.
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abstract = "TCR stimulation results in the tyrosine phosphorylation of a number of cellular substrates. We have recently identified a 70-kDa protein tyrosine kinase, ZAP-70, which associates with the human TCR ζ-chain after TCR stimulation. We report here the isolation and sequence of a cDNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93{\%} amino acid identity and are homologous to the 72-kDa protein tyrosine kinase Syk. Syk has been implicated in the signal transduction pathways of the B cell membrane Ig and high affinity IgE receptors, FcεRI. 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 populations, with the level of expression being comparable to that found in both CD4+ and CD8+ peripheral T cells. Although Syk protein is also 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 cells 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 that 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 for association with the phosphorylated ζ-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development.",
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AU - Chan, Andrew C.

AU - Van Oers A, Nicolai S C

AU - Tran, Annie

AU - Turka, Larry

AU - Law, Che Leung

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