Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich

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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Stine Granum1, Vibeke Sundvold-Gjerstad, Ke-Zheng Dai

  • 1Department of Anatomy, Institute of Basic Medical Sciences, Box 1105, Blindern, N-0317 Oslo, Norway. stine.granum@medisin.uio.no

BMC Immunology
|July 15, 2006
PubMed
Abstract

Insights

The activation induced T cell specific adapter protein (TSAd) interacts with Lck in CD4+ T cells. Alternative splicing of SH2D2A transcripts alters TSAd

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The activation induced T cell specific adapter protein (TSAd), encoded by SH2D2A, modulates Lck activity.
  • The biological significance of TSAd mRNA transcript variants is largely unknown.
  • This study investigates SH2D2A transcript expression in activated CD4+ T cells.

Purpose of the Study:

  • To examine the expression of SH2D2A transcripts in activated CD4+ T cells.
  • To utilize SH2D2A variants to identify functionally important regions of TSAd.
  • To elucidate the interaction modes between TSAd and Lck.

Main Methods:

  • Analysis of SH2D2A transcript expression in CD4+ T cells.
  • Investigation of TSAd-Lck interactions using ex vivo human CD4+ T cells.
  • Mapping of TSAd regions responsible for Lck binding and modulation.

Main Results:

  • TSAd interacts with Lck in human CD4+ T cells through multiple modes.
  • Specific TSAd regions (aa239-256 and aa239-334) mediate binding to Lck domains.
  • SH2D2A exon 7 is crucial for TSAd-Lck interaction, Lck activity modulation, and nuclear translocation.
  • All five SH2D2A transcripts are expressed in stimulated CD4+ T cells.

Conclusions:

  • TSAd and Lck interact via multiple domains in CD4+ T cells.
  • Alternative splicing of SH2D2A exon 7 generates truncated TSAd with altered Lck modulation.
  • The role of differential alternative splicing in regulating TSAd function requires further investigation.

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