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  The Role of the Syk/Shp-1 Kinase-Phosphatase Equilibrium in B Cell Development and Signaling

Alsadeq, A., Hobeika, E., Medgyesi, D., Kläsener, K., & Reth, M. (2014). The Role of the Syk/Shp-1 Kinase-Phosphatase Equilibrium in B Cell Development and Signaling. The Journal of Immunology, 193, 268-276.

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Alsadeq, Ameera1, Autor           
Hobeika, Elias1, Autor           
Medgyesi, David1, Autor           
Kläsener, Kathrin1, Autor           
Reth, Michael1, 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: Signal transduction from the BCR is regulated by the equilibrium between kinases (e.g., spleen tyrosine kinase [Syk]) and phosphatases (e.g., Shp-1). Previous studies showed that Syk-deficient B cells have a developmental block at the pro/pre-B cell stage, whereas a B cell-specific Shp-1 deficiency promoted B-1a cell development and led to autoimmunity. We generated B cell-specific Shp-1 and Syk double-knockout (DKO) mice and compared them to the single-knockout mice deficient for either Syk or Shp-1. Unlike Syk-deficient mice, the DKO mice can generate mature B cells, albeit at >20-fold reduced B cell numbers. The DKO B-2 cells are all Syk-negative, whereas the peritoneal B1 cells of the DKO mice still express Syk, indicating that they require this kinase for their proper development. The DKO B-2 cells cannot be stimulated via the BCR, whereas they are efficiently activated via TLR or CD40. We also found that in DKO pre-B cells, the kinase Zap70 is associated with the pre-BCR, suggesting that Zap70 is important to promote B cell maturation in the absence of Syk and SHP-1. Together, our data show that a properly balanced kinase/phosphatase equilibrium is crucial for normal B cell development and function.

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Sprache(n): eng - English
 Datum: 2014
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 700133
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Titel: The Journal of Immunology
  Alternativer Titel : J. Immunol.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 193 Artikelnummer: - Start- / Endseite: 268 - 276 Identifikator: -