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

Michael S. Patrick, Hiroyo Oda, Kunihiro Hayakawa, Yoshinori Sato, Koji Eshima, Teruo Kirikae, Shun Ichiro Iemura, Mutsunori Shirai, Takaya Abe, Tohru Natsume, Takehiko Sasazuki, Harumi Suzuki

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51 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)16345-16350
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number38
DOIs
Publication statusPublished - Sep 22 2009

All Science Journal Classification (ASJC) codes

  • General

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    Patrick, M. S., Oda, H., Hayakawa, K., Sato, Y., Eshima, K., Kirikae, T., Iemura, S. I., Shirai, M., Abe, T., Natsume, T., Sasazuki, T., & Suzuki, H. (2009). Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes. Proceedings of the National Academy of Sciences of the United States of America, 106(38), 16345-16350. https://doi.org/10.1073/pnas.0908593106