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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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 Creators:
Herzog, Sebastian1, Author              
Jumaa, Hassan1, Author              
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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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 Abstract: 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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Language(s): eng - English
 Dates: 2007
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 329722
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Title: The Journal of Immunology
  Alternative Title : J. Immunol.
Source Genre: Journal
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Pages: - Volume / Issue: 178 Sequence Number: - Start / End Page: 2336 - 2343 Identifier: -