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Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes.

T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both CD4 and CD8 single positive cells in the thymus was severely inhibited, whereas all other TCR-induced events such as beta-selection, negative selection, peripheral activation, and homeostatic proliferation were unaffected. We found that Gasp constitutively associates with Grb2 via its N-terminal Src homology 3 domain, suggesting that Gasp acts as a thymocyte-specific adaptor for Grb2 or regulates Ras signaling in DP thymocytes. Collectively, we have described a gene called Gasp that is critical for positive selection.

Pubmed ID: 19805304


  • Patrick MS
  • Oda H
  • Hayakawa K
  • Sato Y
  • Eshima K
  • Kirikae T
  • Iemura S
  • Shirai M
  • Abe T
  • Natsume T
  • Sasazuki T
  • Suzuki H


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 22, 2009

Associated Grants


Mesh Terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Line
  • Cytosol
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Immunoprecipitation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Proteins
  • Receptors, Antigen, T-Cell
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen
  • T-Lymphocytes
  • Thymus Gland