The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity

Vibeke Sundvold-Gjerstad, Stine Granum, Tomas Mustelin, Thorny C B Andersen, Tony Berge, Michael J. Shapiro, Virginia M Shapiro, Anne Spurkland, Tor Lea

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

T cell-specific adapter protein (TSAd), encoded by the SH2D2A gene, is expressed in activated T cells. The function of TSAd is as yet unknown. We previously showed that TSAd may modulate T cell receptor-triggered signaling events. TSAd contains a Src homology (SH)2 domain, ten tyrosines and a C-terminal proline-rich region. Here, we show that human TSAd interacts with Lck through the Lck SH2 and SH3 domains and is a substrate for Lck. The TSAd C terminus, including the proline-rich region and five tyrosines, is both necessary and sufficient for TSAd interaction with and phosphorylation by Lck. Expression of TSAd in Jurkat TAg cells results in hyperphosphorylation of endogenous Lck on Y394 and to an even larger extent on Y505, resulting in a reduced Y394/Y505 phosphorylation ratio in these cells. Furthermore, full-length TSAd, but not TSAd lacking the C terminus, inhibits the hyperactive Lck Y505F mutant when both are expressed in Jurkat T cells. In contrast, expression of the TSAd C terminus alone is sufficient to inhibit Lck Y505F in phosphorylating its substrates in Jurkat T cells. Our results indicate that the TSAd C terminus is essential for inhibition of Lck activity by TSAd, and suggest a mechanism for how TSAd may inhibit early T cell activation events.

Original languageEnglish (US)
Pages (from-to)1612-1620
Number of pages9
JournalEuropean Journal of Immunology
Volume35
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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T-Lymphocytes
Proteins
Protein C
Jurkat Cells
src Homology Domains
Proline
Tyrosine
Phosphorylation
T-Cell Antigen Receptor

Keywords

  • Adapter protein
  • Lck
  • SH2D2A
  • Signal transduction
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

Sundvold-Gjerstad, V., Granum, S., Mustelin, T., Andersen, T. C. B., Berge, T., Shapiro, M. J., ... Lea, T. (2005). The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. European Journal of Immunology, 35(5), 1612-1620. https://doi.org/10.1002/eji.200425638

The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. / Sundvold-Gjerstad, Vibeke; Granum, Stine; Mustelin, Tomas; Andersen, Thorny C B; Berge, Tony; Shapiro, Michael J.; Shapiro, Virginia M; Spurkland, Anne; Lea, Tor.

In: European Journal of Immunology, Vol. 35, No. 5, 05.2005, p. 1612-1620.

Research output: Contribution to journalArticle

Sundvold-Gjerstad, V, Granum, S, Mustelin, T, Andersen, TCB, Berge, T, Shapiro, MJ, Shapiro, VM, Spurkland, A & Lea, T 2005, 'The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity', European Journal of Immunology, vol. 35, no. 5, pp. 1612-1620. https://doi.org/10.1002/eji.200425638
Sundvold-Gjerstad, Vibeke ; Granum, Stine ; Mustelin, Tomas ; Andersen, Thorny C B ; Berge, Tony ; Shapiro, Michael J. ; Shapiro, Virginia M ; Spurkland, Anne ; Lea, Tor. / The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. In: European Journal of Immunology. 2005 ; Vol. 35, No. 5. pp. 1612-1620.
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