Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding
Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that contr...
Ausführliche Beschreibung
Autor*in: |
Shani, Gidi [verfasserIn] Henis‐Korenblit, Sivan [verfasserIn] Jona, Ghil [verfasserIn] Gileadi, Opher [verfasserIn] Eisenstein, Miriam [verfasserIn] Ziv, Tamar [verfasserIn] Admon, Arie [verfasserIn] Kimchi, Adi [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2001 |
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Schlagwörter: |
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Anmerkung: |
© European Molecular Biology Organization 2001 |
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Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 20(2001), 5 vom: 01. März, Seite 1099-1113 |
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Übergeordnetes Werk: |
volume:20 ; year:2001 ; number:5 ; day:01 ; month:03 ; pages:1099-1113 |
Links: |
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DOI / URN: |
10.1093/emboj/20.5.1099 |
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Katalog-ID: |
SPR057854653 |
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100 | 1 | |a Shani, Gidi |e verfasserin |4 aut | |
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520 | |a Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. | ||
650 | 4 | |a apoptosis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Ca |7 (dpeaa)DE-He213 | |
650 | 4 | |a calmodulin kinases |7 (dpeaa)DE-He213 | |
650 | 4 | |a DRP‐1 |7 (dpeaa)DE-He213 | |
650 | 4 | |a negative autophosphorylation |7 (dpeaa)DE-He213 | |
700 | 1 | |a Henis‐Korenblit, Sivan |e verfasserin |4 aut | |
700 | 1 | |a Jona, Ghil |e verfasserin |4 aut | |
700 | 1 | |a Gileadi, Opher |e verfasserin |4 aut | |
700 | 1 | |a Eisenstein, Miriam |e verfasserin |4 aut | |
700 | 1 | |a Ziv, Tamar |e verfasserin |4 aut | |
700 | 1 | |a Admon, Arie |e verfasserin |4 aut | |
700 | 1 | |a Kimchi, Adi |e verfasserin |4 aut | |
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10.1093/emboj/20.5.1099 doi (DE-627)SPR057854653 (SPR)20.5.1099-e DE-627 ger DE-627 rakwb eng Shani, Gidi verfasserin aut Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding 2001 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2001 Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 Henis‐Korenblit, Sivan verfasserin aut Jona, Ghil verfasserin aut Gileadi, Opher verfasserin aut Eisenstein, Miriam verfasserin aut Ziv, Tamar verfasserin aut Admon, Arie verfasserin aut Kimchi, Adi verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 20(2001), 5 vom: 01. März, Seite 1099-1113 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 https://dx.doi.org/10.1093/emboj/20.5.1099 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 20 2001 5 01 03 1099-1113 |
spelling |
10.1093/emboj/20.5.1099 doi (DE-627)SPR057854653 (SPR)20.5.1099-e DE-627 ger DE-627 rakwb eng Shani, Gidi verfasserin aut Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding 2001 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2001 Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 Henis‐Korenblit, Sivan verfasserin aut Jona, Ghil verfasserin aut Gileadi, Opher verfasserin aut Eisenstein, Miriam verfasserin aut Ziv, Tamar verfasserin aut Admon, Arie verfasserin aut Kimchi, Adi verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 20(2001), 5 vom: 01. März, Seite 1099-1113 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 https://dx.doi.org/10.1093/emboj/20.5.1099 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 20 2001 5 01 03 1099-1113 |
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10.1093/emboj/20.5.1099 doi (DE-627)SPR057854653 (SPR)20.5.1099-e DE-627 ger DE-627 rakwb eng Shani, Gidi verfasserin aut Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding 2001 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2001 Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 Henis‐Korenblit, Sivan verfasserin aut Jona, Ghil verfasserin aut Gileadi, Opher verfasserin aut Eisenstein, Miriam verfasserin aut Ziv, Tamar verfasserin aut Admon, Arie verfasserin aut Kimchi, Adi verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 20(2001), 5 vom: 01. März, Seite 1099-1113 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 https://dx.doi.org/10.1093/emboj/20.5.1099 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 20 2001 5 01 03 1099-1113 |
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10.1093/emboj/20.5.1099 doi (DE-627)SPR057854653 (SPR)20.5.1099-e DE-627 ger DE-627 rakwb eng Shani, Gidi verfasserin aut Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding 2001 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2001 Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 Henis‐Korenblit, Sivan verfasserin aut Jona, Ghil verfasserin aut Gileadi, Opher verfasserin aut Eisenstein, Miriam verfasserin aut Ziv, Tamar verfasserin aut Admon, Arie verfasserin aut Kimchi, Adi verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 20(2001), 5 vom: 01. März, Seite 1099-1113 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 https://dx.doi.org/10.1093/emboj/20.5.1099 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 20 2001 5 01 03 1099-1113 |
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10.1093/emboj/20.5.1099 doi (DE-627)SPR057854653 (SPR)20.5.1099-e DE-627 ger DE-627 rakwb eng Shani, Gidi verfasserin aut Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding 2001 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2001 Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 Henis‐Korenblit, Sivan verfasserin aut Jona, Ghil verfasserin aut Gileadi, Opher verfasserin aut Eisenstein, Miriam verfasserin aut Ziv, Tamar verfasserin aut Admon, Arie verfasserin aut Kimchi, Adi verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 20(2001), 5 vom: 01. März, Seite 1099-1113 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 https://dx.doi.org/10.1093/emboj/20.5.1099 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 20 2001 5 01 03 1099-1113 |
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Enthalten in The EMBO Journal 20(2001), 5 vom: 01. März, Seite 1099-1113 volume:20 year:2001 number:5 day:01 month:03 pages:1099-1113 |
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apoptosis Ca calmodulin kinases DRP‐1 negative autophosphorylation |
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Shani, Gidi @@aut@@ Henis‐Korenblit, Sivan @@aut@@ Jona, Ghil @@aut@@ Gileadi, Opher @@aut@@ Eisenstein, Miriam @@aut@@ Ziv, Tamar @@aut@@ Admon, Arie @@aut@@ Kimchi, Adi @@aut@@ |
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It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. 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|
author |
Shani, Gidi |
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Shani, Gidi misc apoptosis misc Ca misc calmodulin kinases misc DRP‐1 misc negative autophosphorylation Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding |
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1460-2075 |
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Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding apoptosis (dpeaa)DE-He213 Ca (dpeaa)DE-He213 calmodulin kinases (dpeaa)DE-He213 DRP‐1 (dpeaa)DE-He213 negative autophosphorylation (dpeaa)DE-He213 |
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misc apoptosis misc Ca misc calmodulin kinases misc DRP‐1 misc negative autophosphorylation |
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misc apoptosis misc Ca misc calmodulin kinases misc DRP‐1 misc negative autophosphorylation |
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misc apoptosis misc Ca misc calmodulin kinases misc DRP‐1 misc negative autophosphorylation |
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Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding |
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Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding |
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Shani, Gidi Henis‐Korenblit, Sivan Jona, Ghil Gileadi, Opher Eisenstein, Miriam Ziv, Tamar Admon, Arie Kimchi, Adi |
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autophosphorylation restrains the apoptotic activity of drp‐1 kinase by controlling dimerization and calmodulin binding |
title_auth |
Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding |
abstract |
Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. © European Molecular Biology Organization 2001 |
abstractGer |
Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. © European Molecular Biology Organization 2001 |
abstract_unstemmed |
Abstract DRP‐1 is a pro‐apoptotic $ Ca^{2+} $/calmodulin (CaM)‐regulated serine/threonine kinase, recently isolated as a novel member of the DAP‐kinase family of proteins. It contains a short extra‐catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro‐apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP‐1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor‐α death receptors, increases the formation of DRP‐1 dimers, facilitates the binding to CaM and activates the pro‐apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP‐1, and a target for efficient activation of the kinase by various apoptotic stimuli. © European Molecular Biology Organization 2001 |
collection_details |
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container_issue |
5 |
title_short |
Autophosphorylation restrains the apoptotic activity of DRP‐1 kinase by controlling dimerization and calmodulin binding |
url |
https://dx.doi.org/10.1093/emboj/20.5.1099 |
remote_bool |
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author2 |
Henis‐Korenblit, Sivan Jona, Ghil Gileadi, Opher Eisenstein, Miriam Ziv, Tamar Admon, Arie Kimchi, Adi |
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Henis‐Korenblit, Sivan Jona, Ghil Gileadi, Opher Eisenstein, Miriam Ziv, Tamar Admon, Arie Kimchi, Adi |
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doi_str |
10.1093/emboj/20.5.1099 |
up_date |
2024-10-18T04:52:27.122Z |
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|
score |
7.40189 |