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  The N Terminus of the Non-T Cell Activation Linker (NTAL) Confers Inhbitory Effects on Pre-B Cell Differentiation

Herzog, S., & Jumaa, H. (2007). The N Terminus of the Non-T Cell Activation Linker (NTAL) Confers Inhbitory Effects on Pre-B Cell Differentiation. The Journal of Immunology, 178, 2336-2343.

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Herzog, Sebastian1, Autor           
Jumaa, Hassan1, Autor           
Affiliations:
1Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              

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 Zusammenfassung: SLP-65 and the linker for activation of T cells (LAT) are central adaptor proteins that link the activated pre-BCR to downstream events in pre-B cells. Recently, a new transmembrane adaptor called NTAL/LAB/LAT2 (hereafter called NTAL for non-T cell activation linker) with striking functional and structural similarity to LAT has been identified in B cells. In this study, we compare the function of NTAL and LAT in pre-BCR signaling and show that, in contrast to LAT, NTAL does not induce pre-BCR down-regulation, calcium flux, or pre-B cell differentiation. To test whether differences between NTAL-mediated and LAT-mediated signaling are caused by the missing phospholipase C (PLC)-γ binding motif in NTAL, we inserted the PLC-γ1/2 binding motif of LAT into NTAL. This insertion rendered NTAL capable of activating pre-BCR down-regulation and calcium flux. Unexpectedly however, the ability of NTAL to induce calcium flux was not sufficient to promote pre-B cell differentiation, suggesting that the PLC-γ binding motif has only partial effects on NTAL-mediated pre-BCR signaling. By generating chimeric swap mutants, we identified the N terminus of NTAL as an inhibitory domain that prevents pre-B cell differentiation while allowing pre-BCR down-regulation and receptor-mediated calcium flux. Our data suggest that, in addition to the missing PLC-γ1/2 binding motif, the N terminus is responsible for the functional differences between NTAL and LAT in pre-B cells.

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Sprache(n): eng - English
 Datum: 2007
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 329722
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Titel: The Journal of Immunology
  Alternativer Titel : J. Immunol.
Genre der Quelle: Zeitschrift
 Urheber:
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 178 Artikelnummer: - Start- / Endseite: 2336 - 2343 Identifikator: -