Skip to main content

Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line.

Publication ,  Journal Article
Williams, BL; Schreiber, KL; Zhang, W; Wange, RL; Samelson, LE; Leibson, PJ; Abraham, RT
Published in: Mol Cell Biol
March 1998

T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development. However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered by the lack of a suitable T-cell model for biochemical and genetic analyses. In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driven transcription. These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells. However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation. Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 1998

Volume

18

Issue

3

Start / End Page

1388 / 1399

Location

United States

Related Subject Headings

  • ZAP-70 Protein-Tyrosine Kinase
  • Transcriptional Activation
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Antigen, T-Cell
  • Receptor Protein-Tyrosine Kinases
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Jurkat Cells
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Williams, B. L., Schreiber, K. L., Zhang, W., Wange, R. L., Samelson, L. E., Leibson, P. J., & Abraham, R. T. (1998). Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Mol Cell Biol, 18(3), 1388–1399. https://doi.org/10.1128/MCB.18.3.1388
Williams, B. L., K. L. Schreiber, W. Zhang, R. L. Wange, L. E. Samelson, P. J. Leibson, and R. T. Abraham. “Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line.Mol Cell Biol 18, no. 3 (March 1998): 1388–99. https://doi.org/10.1128/MCB.18.3.1388.
Williams BL, Schreiber KL, Zhang W, Wange RL, Samelson LE, Leibson PJ, et al. Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Mol Cell Biol. 1998 Mar;18(3):1388–99.
Williams, B. L., et al. “Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line.Mol Cell Biol, vol. 18, no. 3, Mar. 1998, pp. 1388–99. Pubmed, doi:10.1128/MCB.18.3.1388.
Williams BL, Schreiber KL, Zhang W, Wange RL, Samelson LE, Leibson PJ, Abraham RT. Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Mol Cell Biol. 1998 Mar;18(3):1388–1399.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 1998

Volume

18

Issue

3

Start / End Page

1388 / 1399

Location

United States

Related Subject Headings

  • ZAP-70 Protein-Tyrosine Kinase
  • Transcriptional Activation
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Antigen, T-Cell
  • Receptor Protein-Tyrosine Kinases
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Jurkat Cells
  • Humans