title: A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development.
abstract: Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the alphabeta T cell lineage. In contrast to the gammadelta TCR, the pre-TCR localizes cell-autonomously to membrane rafts, where it appears to signal in a constitutive and ligand-independent manner. We addressed here the role played by structural features specific to the cytoplasmic domain of the pre-TCRalpha chain (pTalpha). More specifically, we examined a COOH-terminal proline-rich sequence that might play a role in signal transduction and a juxtamembrane cysteine residue that could be a target for palmitoylation, thus allowing spontaneous raft localization. Expression of pTalpha mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTalpha cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function.
authors.affiliation: Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
authors.forename: Christine
authors.initials: C
authors.lastname: Borowski
authors.forename: Fotini
authors.initials: F
authors.lastname: Gounari
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Lacorazza
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Zugich
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000818:Animals; D002455:Cell Division / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha