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Publication : In vivo functional mapping of the conserved protein domains within murine Themis1.

First Author  Zvezdova E Year  2014
Journal  Immunol Cell Biol Volume  92
Issue  8 Pages  721-8
PubMed ID  24935457 Mgi Jnum  J:318795
Mgi Id  MGI:6858734 Doi  10.1038/icb.2014.43
Citation  Zvezdova E, et al. (2014) In vivo functional mapping of the conserved protein domains within murine Themis1. Immunol Cell Biol 92(8):721-8
abstractText  Thymocyte development requires the coordinated input of signals that originate from numerous cell surface molecules. Although the majority of thymocyte signal-initiating receptors are lineage-specific, most trigger 'ubiquitous' downstream signaling pathways. T-lineage-specific receptors are coupled to these signaling pathways by lymphocyte-restricted adapter molecules. We and others recently identified a new putative adapter protein, Themis1, whose expression is largely restricted to the T lineage. Mice lacking Themis1 exhibit a severe block in thymocyte development and a striking paucity of mature T cells revealing a critical role for Themis1 in T-cell maturation. Themis1 orthologs contain three conserved domains: a proline-rich region (PRR) that binds to the ubiquitous cytosolic adapter Grb2, a nuclear localization sequence (NLS), and two copies of a novel cysteine-containing globular (CABIT) domain. In the present study, we evaluated the functional importance of each of these motifs by retroviral reconstitution of Themis1(-/-) progenitor cells. The results demonstrate an essential requirement for the PRR and NLS motifs but not the conserved CABIT cysteines for Themis1 function.
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