Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment

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Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment

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Title: Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment
Author: Matsumoto, H; Murakami, Y; Kataoka, K; Lin, H; Connor, K M; Miller, J W; Zhou, D; Avruch, J; Vavvas, D G

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Citation: Matsumoto, H, Y Murakami, K Kataoka, H Lin, K M Connor, J W Miller, D Zhou, J Avruch, and D G Vavvas. 2014. “Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment.” Cell Death & Disease 5 (5): e1269. doi:10.1038/cddis.2014.218. http://dx.doi.org/10.1038/cddis.2014.218.
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Abstract: Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1−/− and MST2−/− mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2−/− mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2−/− mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2−/− mice post-RD. Retinas of MST2−/− mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2−/− mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target.
Published Version: doi:10.1038/cddis.2014.218
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047884/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406658
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