Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease

Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling...
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Autor*in:	Shott, Rory H [verfasserIn] Majer, Anna Frost, Kathy L Booth, Stephanie A Schang, Luis M

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	Prion disease Kinomics Protein kinase Multiplex Western blots CaMK4β CREB MST1

Anmerkung:	© Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Virology journal - London : BioMed Central, 2004, 11(2014), 1 vom: 02. Sept.
Übergeordnetes Werk:	volume:11 ; year:2014 ; number:1 ; day:02 ; month:09

Links:	Volltext

DOI / URN:	10.1186/1743-422X-11-160

Katalog-ID:	SPR029259347

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520			\|a Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times.
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650		4	\|a MST1 \|7 (dpeaa)DE-He213
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allfields	10.1186/1743-422X-11-160 doi (DE-627)SPR029259347 (SPR)1743-422X-11-160-e DE-627 ger DE-627 rakwb eng Shott, Rory H verfasserin aut Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213 Majer, Anna aut Frost, Kathy L aut Booth, Stephanie A aut Schang, Luis M aut Enthalten in Virology journal London : BioMed Central, 2004 11(2014), 1 vom: 02. Sept. (DE-627)394165004 (DE-600)2160640-7 1743-422X nnns volume:11 year:2014 number:1 day:02 month:09 https://dx.doi.org/10.1186/1743-422X-11-160 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2014 1 02 09
spelling	10.1186/1743-422X-11-160 doi (DE-627)SPR029259347 (SPR)1743-422X-11-160-e DE-627 ger DE-627 rakwb eng Shott, Rory H verfasserin aut Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213 Majer, Anna aut Frost, Kathy L aut Booth, Stephanie A aut Schang, Luis M aut Enthalten in Virology journal London : BioMed Central, 2004 11(2014), 1 vom: 02. Sept. (DE-627)394165004 (DE-600)2160640-7 1743-422X nnns volume:11 year:2014 number:1 day:02 month:09 https://dx.doi.org/10.1186/1743-422X-11-160 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2014 1 02 09
allfields_unstemmed	10.1186/1743-422X-11-160 doi (DE-627)SPR029259347 (SPR)1743-422X-11-160-e DE-627 ger DE-627 rakwb eng Shott, Rory H verfasserin aut Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213 Majer, Anna aut Frost, Kathy L aut Booth, Stephanie A aut Schang, Luis M aut Enthalten in Virology journal London : BioMed Central, 2004 11(2014), 1 vom: 02. Sept. (DE-627)394165004 (DE-600)2160640-7 1743-422X nnns volume:11 year:2014 number:1 day:02 month:09 https://dx.doi.org/10.1186/1743-422X-11-160 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2014 1 02 09
allfieldsGer	10.1186/1743-422X-11-160 doi (DE-627)SPR029259347 (SPR)1743-422X-11-160-e DE-627 ger DE-627 rakwb eng Shott, Rory H verfasserin aut Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213 Majer, Anna aut Frost, Kathy L aut Booth, Stephanie A aut Schang, Luis M aut Enthalten in Virology journal London : BioMed Central, 2004 11(2014), 1 vom: 02. Sept. (DE-627)394165004 (DE-600)2160640-7 1743-422X nnns volume:11 year:2014 number:1 day:02 month:09 https://dx.doi.org/10.1186/1743-422X-11-160 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2014 1 02 09
allfieldsSound	10.1186/1743-422X-11-160 doi (DE-627)SPR029259347 (SPR)1743-422X-11-160-e DE-627 ger DE-627 rakwb eng Shott, Rory H verfasserin aut Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213 Majer, Anna aut Frost, Kathy L aut Booth, Stephanie A aut Schang, Luis M aut Enthalten in Virology journal London : BioMed Central, 2004 11(2014), 1 vom: 02. Sept. (DE-627)394165004 (DE-600)2160640-7 1743-422X nnns volume:11 year:2014 number:1 day:02 month:09 https://dx.doi.org/10.1186/1743-422X-11-160 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2014 1 02 09
language	English
source	Enthalten in Virology journal 11(2014), 1 vom: 02. Sept. volume:11 year:2014 number:1 day:02 month:09
sourceStr	Enthalten in Virology journal 11(2014), 1 vom: 02. Sept. volume:11 year:2014 number:1 day:02 month:09
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Prion disease Kinomics Protein kinase Multiplex Western blots CaMK4β CREB MST1
isfreeaccess_bool	true
container_title	Virology journal
authorswithroles_txt_mv	Shott, Rory H @@aut@@ Majer, Anna @@aut@@ Frost, Kathy L @@aut@@ Booth, Stephanie A @@aut@@ Schang, Luis M @@aut@@
publishDateDaySort_date	2014-09-02T00:00:00Z
hierarchy_top_id	394165004
id	SPR029259347
language_de	englisch
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. 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author	Shott, Rory H
spellingShingle	Shott, Rory H misc Prion disease misc Kinomics misc Protein kinase misc Multiplex Western blots misc CaMK4β misc CREB misc MST1 Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease
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topic_title	Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease Prion disease (dpeaa)DE-He213 Kinomics (dpeaa)DE-He213 Protein kinase (dpeaa)DE-He213 Multiplex Western blots (dpeaa)DE-He213 CaMK4β (dpeaa)DE-He213 CREB (dpeaa)DE-He213 MST1 (dpeaa)DE-He213
topic	misc Prion disease misc Kinomics misc Protein kinase misc Multiplex Western blots misc CaMK4β misc CREB misc MST1
topic_unstemmed	misc Prion disease misc Kinomics misc Protein kinase misc Multiplex Western blots misc CaMK4β misc CREB misc MST1
topic_browse	misc Prion disease misc Kinomics misc Protein kinase misc Multiplex Western blots misc CaMK4β misc CREB misc MST1
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title	Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease
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title_full	Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease
author_sort	Shott, Rory H
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author_browse	Shott, Rory H Majer, Anna Frost, Kathy L Booth, Stephanie A Schang, Luis M
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author-letter	Shott, Rory H
doi_str_mv	10.1186/1743-422X-11-160
title_sort	activation of pro-survival camk4β/creb and pro-death mst1 signaling at early and late times during a mouse model of prion disease
title_auth	Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease
abstract	Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo. Methods Mice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states. Results Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi. Conclusion Pro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times. © Shott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease
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Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease

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