Grb2 associated binder 2 couples B-cell receptor to cell survival

Máté Maus, Dávid Medgyesi, Dorottya Kövesdi, Dorottya Csuka, Gábor Koncz, Gabriella Sármay

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

B-cell fate during maturation and the germinal center reaction is regulated through the strength and the duration of the B-cell receptor signal. Signaling pathways discriminating between apoptosis and survival in B cells are keys in understanding adaptive immunity. Gab2 is a member of the Gab/Dos adaptor protein family. It has been shown in several model systems that Gab/Dos family members may regulate both the anti-apoptotic PI3-K/Akt and the mitogenic Ras/MAPK pathways, still their role in B-cells have not been investigated in detail. Here we studied the role of Gab2 in B-cell receptor mediated signaling. We have shown that BCR crosslinking induces the marked phosphorylation of Gab2 through both Lyn and Syk kinases. Subsequently Gab2 recruits p85 regulatory subunit of PI3-K, and SHP-2. Our results revealed that Ig-alpha/Ig-beta, signal transducing unit of the B-cell receptor, may function as scaffold recruiting Gab2 to the signalosome. Overexpression of Gab2 in A20 cells demonstrated that Gab2 is a regulator of the PI3-K/Akt but not that of the Ras/MAPK pathway in B cells. Accordingly to the elevated Akt phosphorylation, overexpression of wild-type Gab2 in A20 cells suppressed Fas-mediated apoptosis, and enhanced BCR-mediated rescue from Fas-induced cell death. Although PH-domain has only a stabilizing effect on membrane recruitment of Gab2, it is indispensable in mediating its anti-apoptotic effect.

Original languageEnglish
Pages (from-to)220-227
Number of pages8
JournalCellular Signalling
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • B-cell
  • Gab2 adaptor/scaffolding protein
  • PH domain
  • Phosphorylation
  • Signaling
  • Survival

ASJC Scopus subject areas

  • Cell Biology

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