title: In vivo functional mapping of the conserved protein domains within murine Themis1.
abstract: 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.
authors.affiliation: Section on Cellular and Developmental Biology, Program on Genomics of Differentiation, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Zvezdova
authors.affiliation: Section on Cellular and Developmental Biology, Program on Genomics of Differentiation, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Section on Cellular and Developmental Biology, Program on Genomics of Differentiation, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Dalal
authors.initials: D
authors.lastname: El-Khoury
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Valarie
authors.initials: V
authors.lastname: Barr
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Itoro
authors.initials: I
authors.lastname: Akpan
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Samelson
authors.affiliation: Section on Cellular and Developmental Biology, Program on Genomics of Differentiation, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C544192:themis protein, mouse