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The small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells.

Authors :
de Gorter DJ
Reijmers RM
Beuling EA
Naber HP
Kuil A
Kersten MJ
Pals ST
Spaargaren M
Source :
Blood [Blood] 2008 Apr 01; Vol. 111 (7), pp. 3364-72. Date of Electronic Publication: 2008 Jan 28.
Publication Year :
2008

Abstract

Chemokine-controlled migration plays a critical role in B-cell development, differentiation, and function, as well as in the pathogenesis of B-cell malignancies, including the plasma cell neoplasm multiple myeloma (MM). Here, we demonstrate that stimulation of B cells and MM cells with the chemokine stromal cell-derived factor-1 (SDF-1) induces strong migration and activation of the Ras-like GTPase Ral. Inhibition of Ral, by expression of the dominant negative RalN28 mutant or of RalBPDeltaGAP, a Ral effector mutant that sequesters active Ral, results in impaired SDF-1-induced migration of B cells and MM cells. Of the 2 Ral isoforms, RalA and RalB, RalB was found to mediate SDF-1-induced migration. We have recently shown that Btk, PLCgamma2, and Lyn/Syk mediate SDF-1-controlled B-cell migration; however, SDF-1-induced Ral activation is not affected in B cells deficient in these proteins. In addition, treatment with pharmacological inhibitors against PI3K and PLC or expression of dominant-negative Ras did not impair SDF-1-induced Ral activation. Taken together, these results reveal a novel function for Ral, that is, regulation of SDF-1-induced migration of B cells and MM cells, thereby providing new insights into the control of B-cell homeostasis, trafficking, and function, as well as into the pathogenesis of MM.

Details

Language :
English
ISSN :
0006-4971
Volume :
111
Issue :
7
Database :
MEDLINE
Journal :
Blood
Publication Type :
Academic Journal
Accession number :
18227351
Full Text :
https://doi.org/10.1182/blood-2007-08-106583