Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells.
The activity of Bad, a pro-apoptotic protein, is regulated by reversible phosphorylation. Moreover, sequestration of Bad within subcellular compartments may be a new mechanism of apoptosis regulation. In this study, we report that Bad interacts with 14-3-3 protein in WEHI-231 immature B cells. This association is disrupted following BCR stimulation in correlation with Bad translocation to mitochondria and apoptosis. Confocal microscopy was further used to examine the co-localization of Bad with lipid rafts in WEHI-231 and murineex vivoB cells. Bad was found colocalized to lipid rafts in freshly isolated mature B lymphocytes, in contrast to immature cells. Finally, co-immunoprecipitation experiments performed on WEHI-231 B cells revealed that PP1alpha interacts with Bcl-2 and Bad, and dissociation of the complex was found correlated with appearance of apoptosis. Bcl-2 seemed to be required to assemble the complex which may regulate Bad phosphorylation status and consequently cell survival. Collectively, present data outline the role of Bad trafficking in the BCR-mediated apoptosis and suggest that differences in intracellular Bad trafficking may be involved in the differential outcome of BCR signaling.
Malissein
E
E
EA 3842, "Homéostasie Cellulaire & Pathologies," Limoges, France.
Verdier
M
M
Ratinaud
M H
MH
Troutaud
D
D
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D051379:Mice; D021381:Protein Transport / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
D048948:14-3-3 Proteins; C494820:Bad protein, mouse; D011947:Receptors, Antigen, B-Cell; D051025:bcl-Associated Death Protein