Regulation of Bad Phosphorylation and Association with Bcl-xL by the MAPK/Erk Kinase

Scheid, Michael P.; Schubert, Kathryn; Duronio, Vincent

doi:10.1074/jbc.274.43.31108

Cited by 362 publications

(318 citation statements)

References 52 publications

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“…Both Akt and ERK can phosphorylate BAD (41,42). We observed SAA-induced phosphorylation of BAD at Ser 112 and Ser 136 consistent with activation of ERK and Akt, respectively.…”

Section: Discussionsupporting

confidence: 69%

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Kebir

József

Khreiss

et al. 2007

The Journal of Immunology

127

157

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Myeloperoxidase (MPO), a heme protein abundantly expressed in the azurophilic granules in neutrophils generates cytotoxic oxidants and signals through the adhesion molecule CD11b/CD18 (Mac‐1) to activate and rescue neutrophils from apoptosis. Since aspirin‐triggered 15‐epi‐lipoxin A4 (15‐epi‐LXA4) inhibits Mac‐1‐mediated neutrophil adhesion, we studied its impact on MPO suppression of neutrophil apoptosis. Pretreatment of neutrophils with 15‐epi‐LXA4 or its metabolically stable analog 15‐epi‐16‐p‐fluorophenoxy‐LXA4 through downregulation of surface expression of Mac‐1 and inhibition of MPO release overcame the powerful anti‐apoptosis signal from MPO. 15‐epi‐LXA4 promoted apoptosis by attenuating MPO‐induced concurrent activation of ERK and phosphatidylinositol 3‐kinase/Akt‐mediated phosphorylation of Bad and reducing the expression of the anti‐apoptotic protein Mcl‐1. These led to collapse of mitochondrial transmembrane potential, cytochrome c release, resulting in increased caspase‐3 activity. The pro‐apoptotic action of 15‐epi‐LXA4 was predominant over MPO‐mediated effects even when 15‐epi‐LXA4 was added at 4‐hour post‐MPO. 15‐epi‐LXA4 did not inhibit the catalytic activity of MPO. Our results indicate that through overriding the MPO survival signal, aspirin‐triggered lipoxins may prevent neutrophil‐mediated tissue injury. (Grant support: CIHR MOP‐64283).

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“…Both Akt and ERK can phosphorylate BAD (41,42). We observed SAA-induced phosphorylation of BAD at Ser 112 and Ser 136 consistent with activation of ERK and Akt, respectively.…”

Section: Discussionsupporting

confidence: 69%

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Kebir

József

Khreiss

et al. 2007

The Journal of Immunology

127

157

View full text Add to dashboard Cite

show abstract

“…For example, Akt and ERKs phosphorylate Bad on distinct serines blocking its proapoptotic effects. 31,32 They also phosphorylate and inhibit caspase-9 promoting cell survival. 33,34 To conclude about the protective effect of MITC towards thymocytes, we suggested that MITC activated in thymocytes, a 'prosurvival' or 'antiapoptotic' signaling pathway involving especially ERK1/2 but also Akt which is acting upstream of ERK1/2.…”

Section: Discussionmentioning

confidence: 99%

Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways

Panse

Berrih‐Aknin

2005

Cell Death Differ

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Thymic myoid cells correspond to a muscle-like cell population present in the thymic medulla. They are well conserved throughout species evolution, but their biological role is not known. We demonstrated that myoid cells protected thymocytes from apoptosis as evidenced by a strong decrease of annexin-V-FITC positive thymocytes. This effect was (1) specific of myoid cells compared to thymic epithelial cells; (2) dependent on direct cell-to-cell contacts and (3) triggered rapidly after 2 h in cocultures. This protective phenomenon was due to the activation of prosurvival mechanisms. Indeed, myoid cells activated extracellular-regulated kinases (ERK1/2) and Akt in thymocytes. Myoid cells also influenced thymocyte maturation. We observed an increase in CD4 þ and a decrease in CD8 þ single positive (SP) thymocytes when cocultured with myoid cells, independently of a CD8 þ SP increased death or a CD4 þ SP overproliferation. Consequently, thymic myoid cells protect thymocytes from apoptosis and could also modulate their differentiation process.

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“…Not only the expression of Bcl-xL but also the membrane association of proapoptotic Bax is maintained by IL-3, and both are required for cell survival [24]. IL-3 also maintains the hyperphosphorylation of pro-apoptotic Bad both at serine 112 via the MAPK-ERK cascade and at serine 136 via the PI3K-Akt pathway, preventing its binding to BclxL [25,26]. Withdrawal of IL-3, in turn, results in the loss of all these anti-apoptotic signals.…”

Section: Discussionmentioning

confidence: 99%

“…Not only the expression of Bcl-xL but also the membrane association of pro-apoptotic Bax is maintained by IL-3, and both are required for cell survival [24]. IL-3 also maintains hyperphosphorylation of the proapoptotic Bad both at serine 112 via the MAPK-ERK cascade and at serine 136 via the PI3K-Akt pathway, preventing its binding to Bcl-xL [25,26]. Expression of another anti-apoptotic molecule, Bcl-2, is also regulated by IL-3 though the signaling mechanisms are unknown, and the anti-apoptotic potential of Bcl-2 is enhanced by phosphorylation at serine 77 by the MAPK-ERK signaling pathway [27].…”

Section: Introductionmentioning

confidence: 99%

Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation

Yoshikawa

Tasaka

2003

Eur J Immunol

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IL-3-dependent mucosal-like mast cells undergo apoptosis upon withdrawal of IL-3. Generally, the apoptosis is mediated by the activation of caspases and inhibited by addition of the pan-caspase inhibitors z-VAD-FMK or BOC-D-FMK. However, DNA fragmentation, a typical characteristic of apoptosis, is not inhibited by z-VAD-FMK or BOC-D-FMK in mast cell apoptosis. In this study, we demonstrate that the apoptosis of mast cells is mediated by both caspase-dependent and -independent mechanisms. The caspase-independent apoptosis is mediated by the translocation of endonuclease G from mitochondria into nuclei. Withdrawal of IL-3 caused down-regulation of Bcl-xL, resulting in a drop in mitochondrial membrane transition potential followed by the release of cytochrome c and endonuclease G from mitochondria. However, stimulation of mast cells through Toll-like receptor 4 (TLR4) by lipopolysaccharide prevented mast cell apoptosis by inducing expression of Bcl-xL. Moreover, the activation of mast cells by LPS is enhanced in the presence of IFN-+ , which up-regulates the expression of cell surface TLR4. Taken together, these observations provide evidence that mast cells play important roles not only in allergic reactions but also in innate immunity recognizing enterobacteria through TLR4, and are regulated differently from allergic inflammation by Th1 cytokines.

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Regulation of Bad Phosphorylation and Association with Bcl-xL by the MAPK/Erk Kinase

Cited by 362 publications

References 52 publications

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways

Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation

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