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Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes

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    SYSNO ASEP0105347
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JOstatní články
    TitleGrb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes
    TitleGrb2 a NTAL (non-T cell activation linker) tvoří signální okruh regulující Ca(2+) v B lymfocytech
    Author(s) Stork, B. (DE)
    Engelke, M. (DE)
    Frey, J. (DE)
    Hořejší, Václav (UMG-J) RID
    Hamm-Baarke, A. (DE)
    Schraven, B. (DE)
    Kurosaki, T. (JP)
    Wienands, J. (DE)
    Source TitleImmunity. - : Elsevier - ISSN 1074-7613
    Roč. 21, č. 5 (2004), s. 681-691
    Number of pages10 s.
    Languageeng - English
    CountryUS - United States
    KeywordsNTAL ; Grb2 ; lymphocyte
    Subject RIVEC - Immunology
    R&D ProjectsLN00A026 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    CEZAV0Z5052915 - UMG-J
    AnnotationActivation of the B cell antigen receptor triggers phosphorylation of cytoplasmic and transmembrane adaptor proteins such as SLP-65 and NTAL, respectively. Specific phosphoacceptor sites in SLP-65 serve as docking sites for Ca(2+)-mobilizing enzymes Btk and PLC-gamma2. Phosphorylated NTAL recruits the Grb2 linker, but downstream signaling cascades are unclear. We now show that receptor-induced tyrosine phosphorylation of NTAL and concomitant Grb2 complex formation critically modulate the Ca(2+) response without affecting SLP-65 and PLC-gamma2 phosphorylation. Grb2 turned out to play a negative regulatory role, which appears to be eliminated upon binding to NTAL. This allows for a sustained release of intracellular Ca(2+) and is mandatory for subsequent entry of Ca(2+) from extracellular sources. Thus, elevation of Ca(2+) is regulated by at least two signaling modules, the B cell-specific Ca(2+) initiation complex comprising SLP-65, Btk, and PLC-gamma2 and the more ubiquitously expressed NTAL/Grb2 complex, which acts as an amplifier by switching off inhibitory elements
    WorkplaceInstitute of Molecular Genetics
    ContactNikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
    Year of Publishing2010

Number of the records: 1  

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