Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo
Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐lin...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Vanhaesebroeck, Bart [verfasserIn] Higashi, Kyochiro [verfasserIn] Raven, Catherine [verfasserIn] Welham, Melanie [verfasserIn] Anderson, Simon [verfasserIn] Brennan, Paul [verfasserIn] Ward, Stephen G. [verfasserIn] Waterfield, Michael D. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
1999 |
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| Schlagwörter: |
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| Anmerkung: |
© European Molecular Biology Organization 1999 |
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| Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 18(1999), 5 vom: 01. März, Seite 1292-1302 |
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| Übergeordnetes Werk: |
volume:18 ; year:1999 ; number:5 ; day:01 ; month:03 ; pages:1292-1302 |
| Links: |
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| DOI / URN: |
10.1093/emboj/18.5.1292 |
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| Katalog-ID: |
SPR057809313 |
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| 100 | 1 | |a Vanhaesebroeck, Bart |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
| 264 | 1 | |c 1999 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a © European Molecular Biology Organization 1999 | ||
| 520 | |a Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. | ||
| 650 | 4 | |a autophosphorylation |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a phosphoinositide 3‐kinase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a phosphospecific antibodies |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Higashi, Kyochiro |e verfasserin |4 aut | |
| 700 | 1 | |a Raven, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Welham, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Brennan, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Ward, Stephen G. |e verfasserin |4 aut | |
| 700 | 1 | |a Waterfield, Michael D. |e verfasserin |4 aut | |
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| 952 | |d 18 |j 1999 |e 5 |b 01 |c 03 |h 1292-1302 | ||
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1999 |
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1999 |
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10.1093/emboj/18.5.1292 doi (DE-627)SPR057809313 (SPR)18.5.1292-e DE-627 ger DE-627 rakwb eng Vanhaesebroeck, Bart verfasserin aut Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo 1999 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 1999 Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 Higashi, Kyochiro verfasserin aut Raven, Catherine verfasserin aut Welham, Melanie verfasserin aut Anderson, Simon verfasserin aut Brennan, Paul verfasserin aut Ward, Stephen G. verfasserin aut Waterfield, Michael D. verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 18(1999), 5 vom: 01. März, Seite 1292-1302 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 https://dx.doi.org/10.1093/emboj/18.5.1292 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 18 1999 5 01 03 1292-1302 |
| spelling |
10.1093/emboj/18.5.1292 doi (DE-627)SPR057809313 (SPR)18.5.1292-e DE-627 ger DE-627 rakwb eng Vanhaesebroeck, Bart verfasserin aut Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo 1999 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 1999 Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 Higashi, Kyochiro verfasserin aut Raven, Catherine verfasserin aut Welham, Melanie verfasserin aut Anderson, Simon verfasserin aut Brennan, Paul verfasserin aut Ward, Stephen G. verfasserin aut Waterfield, Michael D. verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 18(1999), 5 vom: 01. März, Seite 1292-1302 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 https://dx.doi.org/10.1093/emboj/18.5.1292 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 18 1999 5 01 03 1292-1302 |
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10.1093/emboj/18.5.1292 doi (DE-627)SPR057809313 (SPR)18.5.1292-e DE-627 ger DE-627 rakwb eng Vanhaesebroeck, Bart verfasserin aut Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo 1999 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 1999 Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 Higashi, Kyochiro verfasserin aut Raven, Catherine verfasserin aut Welham, Melanie verfasserin aut Anderson, Simon verfasserin aut Brennan, Paul verfasserin aut Ward, Stephen G. verfasserin aut Waterfield, Michael D. verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 18(1999), 5 vom: 01. März, Seite 1292-1302 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 https://dx.doi.org/10.1093/emboj/18.5.1292 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 18 1999 5 01 03 1292-1302 |
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10.1093/emboj/18.5.1292 doi (DE-627)SPR057809313 (SPR)18.5.1292-e DE-627 ger DE-627 rakwb eng Vanhaesebroeck, Bart verfasserin aut Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo 1999 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 1999 Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 Higashi, Kyochiro verfasserin aut Raven, Catherine verfasserin aut Welham, Melanie verfasserin aut Anderson, Simon verfasserin aut Brennan, Paul verfasserin aut Ward, Stephen G. verfasserin aut Waterfield, Michael D. verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 18(1999), 5 vom: 01. März, Seite 1292-1302 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 https://dx.doi.org/10.1093/emboj/18.5.1292 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 18 1999 5 01 03 1292-1302 |
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10.1093/emboj/18.5.1292 doi (DE-627)SPR057809313 (SPR)18.5.1292-e DE-627 ger DE-627 rakwb eng Vanhaesebroeck, Bart verfasserin aut Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo 1999 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 1999 Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 Higashi, Kyochiro verfasserin aut Raven, Catherine verfasserin aut Welham, Melanie verfasserin aut Anderson, Simon verfasserin aut Brennan, Paul verfasserin aut Ward, Stephen G. verfasserin aut Waterfield, Michael D. verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 18(1999), 5 vom: 01. März, Seite 1292-1302 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 https://dx.doi.org/10.1093/emboj/18.5.1292 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 18 1999 5 01 03 1292-1302 |
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Enthalten in The EMBO Journal 18(1999), 5 vom: 01. März, Seite 1292-1302 volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 |
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Enthalten in The EMBO Journal 18(1999), 5 vom: 01. März, Seite 1292-1302 volume:18 year:1999 number:5 day:01 month:03 pages:1292-1302 |
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autophosphorylation lipid phosphoinositide 3‐kinase phosphospecific antibodies |
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Vanhaesebroeck, Bart @@aut@@ Higashi, Kyochiro @@aut@@ Raven, Catherine @@aut@@ Welham, Melanie @@aut@@ Anderson, Simon @@aut@@ Brennan, Paul @@aut@@ Ward, Stephen G. @@aut@@ Waterfield, Michael D. @@aut@@ |
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The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. 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Vanhaesebroeck, Bart |
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Vanhaesebroeck, Bart misc autophosphorylation misc lipid misc phosphoinositide 3‐kinase misc phosphospecific antibodies Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
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Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo autophosphorylation (dpeaa)DE-He213 lipid (dpeaa)DE-He213 phosphoinositide 3‐kinase (dpeaa)DE-He213 phosphospecific antibodies (dpeaa)DE-He213 |
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Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
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Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
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Vanhaesebroeck, Bart Higashi, Kyochiro Raven, Catherine Welham, Melanie Anderson, Simon Brennan, Paul Ward, Stephen G. Waterfield, Michael D. |
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autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
| title_auth |
Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
| abstract |
Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. © European Molecular Biology Organization 1999 |
| abstractGer |
Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. © European Molecular Biology Organization 1999 |
| abstract_unstemmed |
Abstract Phosphoinositide 3‐kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase‐linked PI3K, p110δ, is characterized and its functional impact assessed. In vitro autophosphorylation of p110δ completely down‐regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C‐terminus of p110δ. Antisera specific for phospho‐Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110δ that is recruited to activated receptors (such as CD28 in T cells) shows a time‐dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039‐phosphorylated p110δ. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110δ itself, are involved in the in vivo phosphorylation of p110δ. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules. © European Molecular Biology Organization 1999 |
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Autophosphorylation of p110δ phosphoinositide 3‐kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo |
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Higashi, Kyochiro Raven, Catherine Welham, Melanie Anderson, Simon Brennan, Paul Ward, Stephen G. Waterfield, Michael D. |
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| score |
7.400222 |