Changes in Bad phosphorylation are correlated with BCR-induced apoptosis of WEHI-231 immature B cells

Malissein, Emilie; Verdier, Mireille; Ratinaud, Marie‐Hélène; Troutaud, Danielle

doi:10.1016/s0300-9084(03)00140-8

Cited by 12 publications

(16 citation statements)

References 44 publications

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“…Phosphorylation of S 136 on BAD (pBAD) by Akt suppresses BAD activity so that pBAD cannot antagonize the pro-survival functions of Bcl-2 and Bcl-xL [47,48]. In this report, we found that IL-4 prevented anti-IgM-mediated deactivation (S 473 dephosphorylation) of Akt ( Figure 6) and maintained pBAD at levels seen in controls.…”

Section: Discussionmentioning

confidence: 65%

“…pAkt activity controls both the expression and activities of multiple pro-apoptotic proteins such as BAD, GSK-3β, IKK, caspase-9 and the forkhead (FKHR) transcription factors [44][45][46]. BAD can perturb the mitochondrion by antagonizing the survival functions of Bcl-2 and Bcl-xL, and phosphorylation of S 136 on BAD (pBAD) by Akt suppresses BAD activity [47,48]. Intriguingly, we found that, in addition to inducing the dephosphorylation of Akt, antiIgM caused a reduction in the phosphorylation of BAD.…”

Section: Effects Of Il-4 Signaling On the Pi-3k/akt Pathway And Protementioning

confidence: 99%

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IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: contribution of the PI-3 kinase/AKT pathway

Carey

Семенова

et al. 2007

Cell Res

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Interleukin-4 (IL-4) promotes lymphocyte survival and protects primary lymphomas from apoptosis. Previous studies reported differential requirements for the signal transducer and activator of transcription 6 (STAT6) and IRS2/phosphatidylinositol 3 kinase (PI-3K) signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis. In this study, we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31, a model B-cell lymphoma line. In CH31, anti-IgM treatment leads to the loss of mitochondrial membrane potential, phospho-Akt, phospho-CDK2, and c-myc protein. These losses are followed by massive induction of p27 Kip1 protein expression, cell cycle arrest, and apoptosis. Strikingly, IL-4 treatment prevented or reversed these changes. Furthermore, IL-4 suppressed the activation of caspases 9 and 3, and, in contrast to previous reports, induced the phosphorylation (deactivation) of BAD. IL-4 treatment also induced expression of BclxL, a STAT6-dependent gene. Pharmacologic inhibitors and dominant inhibitory forms of PI-3K and Akt abrogated the anti-apoptotic function of IL-4. These results suggest that the IL-4 receptor activates several signaling pathways, with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

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Section: Discussionmentioning

confidence: 65%

Section: Effects Of Il-4 Signaling On the Pi-3k/akt Pathway And Protementioning

confidence: 99%

IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: contribution of the PI-3 kinase/AKT pathway

Carey

Семенова

et al. 2007

Cell Res

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“…Opening of the pore, which is regulated by the Bcl-2 family proteins, has been demonstrated to induce depolarization of the transmembrane potential (DW m ), release of apoptogenic factors, and loss of oxidative phosphorylation (11)(12)(13). Notably, Bad, a proapoptotic member of this family which is found inactivated by phosphorylation on serine residues in healthy cells, operates upstream in connecting proximal cell death signals with the mitochondrial cell death machinery (14)(15)(16). Previous studies in old mice reported a more susceptible mitochondrial permeability transition (PT) to activation in immune cells.…”

mentioning

confidence: 99%

Aged mice exhibit distinct peripheral B‐cell phenotypes differing in apoptotic susceptibility: An ex vivo analysis

Verdier¹,

Malissein²,

E³

et al. 2006

Cytometry Pt A

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Background: Age-related changes in the antibody response have been classically associated with alterations in T-cell help, but increasing evidence shows that intrinsic B-cell defects exist. This article analyzes the apoptotic susceptibility of peripheral B-cells in aged and young control mice. Materials and Methods: Freshly isolated lymphocytes from spleen and Peyer's patches (PPs) were labeled for Bcell lineage (B220 1 cells) and germinal center B subset (GCs, B2201 /PNA 1 cells). Alternatively, splenic B-cells purified by MACS were used. Apoptosis was monitored by the Annexin V binding, incorporation of 3,3 0 -dihexyloxacarbocyanine iodide (DiOC 6 (3)), propidium iodide (PI) staining, and morphological changes. Moreover, intracellular Bcl-2 expression and Bad phosphorylation status were also analyzed in B-cells. Results: We showed in aging mice an enhanced Annexin V

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“…PI3K/Akt and PKA) mimicked and/or enhanced BCR-induced cell death, suggesting a contribution of Bad kinase and/or phosphatase activities in BCR-mediated responses. 23 In this study, we report for the first time intracellular trafficking of Bad and its association with partners as a dynamic process regulated by BCR engagement in WEHI-231 cells. We found that the trimolecular complex Bcl-2/PP1α/Bad, considered to function as a Bad phosphatase, was recovered in WEHI-231 B cells, and its dissociation was correlated with the appearance of apoptosis.…”

Section: Introductionmentioning

confidence: 77%

Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells

Malissein¹,

Verdier²,

Ratinaud³

et al. 2006

Apoptosis

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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.

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Changes in Bad phosphorylation are correlated with BCR-induced apoptosis of WEHI-231 immature B cells

Cited by 12 publications

References 44 publications

IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: contribution of the PI-3 kinase/AKT pathway

IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: contribution of the PI-3 kinase/AKT pathway

Aged mice exhibit distinct peripheral B‐cell phenotypes differing in apoptotic susceptibility: An ex vivo analysis

Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells

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