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Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells.

Publication ,  Journal Article
Lindholm, CK; Gylfe, E; Zhang, W; Samelson, LE; Welsh, M
Published in: J Biol Chem
September 24, 1999

Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the TCR zeta-chain in Jurkat cells. We now report that Shb also associates with phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation. Nuclear factor for activation of T cells is a major target for Ras and calcium signaling pathways in T cells following TCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma1 and resulting in the activation of transcription of the interleukin-2 gene.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 24, 1999

Volume

274

Issue

39

Start / End Page

28050 / 28057

Location

United States

Related Subject Headings

  • src Homology Domains
  • Type C Phospholipases
  • Transfection
  • Transcription Factors
  • T-Lymphocytes
  • Recombinant Proteins
  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins
  • Proteins
  • Protein-Tyrosine Kinases
 

Citation

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Lindholm, C. K., Gylfe, E., Zhang, W., Samelson, L. E., & Welsh, M. (1999). Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells. J Biol Chem, 274(39), 28050–28057. https://doi.org/10.1074/jbc.274.39.28050
Lindholm, C. K., E. Gylfe, W. Zhang, L. E. Samelson, and M. Welsh. “Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells.J Biol Chem 274, no. 39 (September 24, 1999): 28050–57. https://doi.org/10.1074/jbc.274.39.28050.
Lindholm, C. K., et al. “Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells.J Biol Chem, vol. 274, no. 39, Sept. 1999, pp. 28050–57. Pubmed, doi:10.1074/jbc.274.39.28050.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 24, 1999

Volume

274

Issue

39

Start / End Page

28050 / 28057

Location

United States

Related Subject Headings

  • src Homology Domains
  • Type C Phospholipases
  • Transfection
  • Transcription Factors
  • T-Lymphocytes
  • Recombinant Proteins
  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins
  • Proteins
  • Protein-Tyrosine Kinases