Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway.
BACKGROUND: Mammalian Ste20-like kinases (MSTs) are the mammalian homologue of Drosophila hippo and play critical roles in regulation of cell death, organ size control, proliferation and tumorigenesis. MSTs exert pro-apoptotic function through cleavage, autophosphorylation and in turn phosphorylatio...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3348883?pdf=render |
| _version_ | 1811260010817126400 |
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| author | Weizhe Liu Junbing Wu Lei Xiao Yujie Bai Aiqin Qu Zheng Zheng Zengqiang Yuan |
| author_facet | Weizhe Liu Junbing Wu Lei Xiao Yujie Bai Aiqin Qu Zheng Zheng Zengqiang Yuan |
| author_sort | Weizhe Liu |
| collection | DOAJ |
| description | BACKGROUND: Mammalian Ste20-like kinases (MSTs) are the mammalian homologue of Drosophila hippo and play critical roles in regulation of cell death, organ size control, proliferation and tumorigenesis. MSTs exert pro-apoptotic function through cleavage, autophosphorylation and in turn phosphorylation of downstream targets, such as Histone H2B and FOXO (Forkhead box O). Previously we reported that protein kinase c-Abl mediates oxidative stress-induced neuronal cell death through phosphorylating MST1 at Y433, which is not conserved among mammalian MST2, Drosophila Hippo and C.elegans cst-1/2. METHODOLOGY/PRINCIPAL FINDINGS: Using immunoblotting, in vitro kinase and cell death assay, we demonstrate that c-Abl kinase phosphorylates MST2 at an evolutionarily conserved site, Y81, within the kinase domain. We further show that the phosphorylation of MST2 by c-Abl leads to the disruption of the interaction with Raf-1 proteins and the enhancement of homodimerization of MST2 proteins. It thereby enhances the MST2 activation and induces neuronal cell death. CONCLUSIONS/SIGNIFICANCE: The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2 suggests that the conserved c-Abl-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death. |
| first_indexed | 2024-04-12T18:41:08Z |
| format | Article |
| id | doaj.art-fefd57f40df44b639b825c0be310fdf7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T18:41:08Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fefd57f40df44b639b825c0be310fdf72022-12-22T03:20:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3656210.1371/journal.pone.0036562Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway.Weizhe LiuJunbing WuLei XiaoYujie BaiAiqin QuZheng ZhengZengqiang YuanBACKGROUND: Mammalian Ste20-like kinases (MSTs) are the mammalian homologue of Drosophila hippo and play critical roles in regulation of cell death, organ size control, proliferation and tumorigenesis. MSTs exert pro-apoptotic function through cleavage, autophosphorylation and in turn phosphorylation of downstream targets, such as Histone H2B and FOXO (Forkhead box O). Previously we reported that protein kinase c-Abl mediates oxidative stress-induced neuronal cell death through phosphorylating MST1 at Y433, which is not conserved among mammalian MST2, Drosophila Hippo and C.elegans cst-1/2. METHODOLOGY/PRINCIPAL FINDINGS: Using immunoblotting, in vitro kinase and cell death assay, we demonstrate that c-Abl kinase phosphorylates MST2 at an evolutionarily conserved site, Y81, within the kinase domain. We further show that the phosphorylation of MST2 by c-Abl leads to the disruption of the interaction with Raf-1 proteins and the enhancement of homodimerization of MST2 proteins. It thereby enhances the MST2 activation and induces neuronal cell death. CONCLUSIONS/SIGNIFICANCE: The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2 suggests that the conserved c-Abl-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death.http://europepmc.org/articles/PMC3348883?pdf=render |
| spellingShingle | Weizhe Liu Junbing Wu Lei Xiao Yujie Bai Aiqin Qu Zheng Zheng Zengqiang Yuan Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. PLoS ONE |
| title | Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. |
| title_full | Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. |
| title_fullStr | Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. |
| title_full_unstemmed | Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. |
| title_short | Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. |
| title_sort | regulation of neuronal cell death by c abl hippo mst2 signaling pathway |
| url | http://europepmc.org/articles/PMC3348883?pdf=render |
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