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

Máté Maus, Dávid Medgyesi, Dorottya Kövesdi, Dorottya Csuka, G. Koncz, G. 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

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Cell Survival
B-Lymphocytes
Phosphorylation
Apoptosis
Germinal Center
Adaptive Immunity
Cell Death
Membranes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Grb2 associated binder 2 couples B-cell receptor to cell survival. / Maus, Máté; Medgyesi, Dávid; Kövesdi, Dorottya; Csuka, Dorottya; Koncz, G.; Sármay, G.

In: Cellular Signalling, Vol. 21, No. 2, 02.2009, p. 220-227.

Research output: Contribution to journalArticle

Maus, Máté ; Medgyesi, Dávid ; Kövesdi, Dorottya ; Csuka, Dorottya ; Koncz, G. ; Sármay, G. / Grb2 associated binder 2 couples B-cell receptor to cell survival. In: Cellular Signalling. 2009 ; Vol. 21, No. 2. pp. 220-227.
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