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 [Proc Natl Acad Sci U S A] Journal article | | Title | Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes. | | Author(s) | Patrick MS, Oda H, Hayakawa K, Sato Y, Eshima K, Kirikae T, Iemura S, Shirai M, Abe T, Natsume T, Sasazuki T, Suzuki H | | Institution | Department of Pathology and Infectious Diseases, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku, Tokyo 162-8655, Japan. | | Source | Proc Natl Acad Sci U S A 2009 Sep 22; 106(38):16345-50. | | 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 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19805304 |
|
|
| |
Advertise on this site.
| | |
|
