Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail
The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulati...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Li, Xiuju [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2016transfer abstract |
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| Umfang: |
11 |
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| Übergeordnetes Werk: |
Enthalten in: Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre - Alizadeh, H. ELSEVIER, 2015, New York, NY [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:99 ; year:2016 ; pages:65-75 ; extent:11 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.yjmcc.2016.08.014 |
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ELV030128382 |
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| 245 | 1 | 0 | |a Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail |
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| 520 | |a The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. | ||
| 520 | |a The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. | ||
| 700 | 1 | |a Augustine, Aruna |4 oth | |
| 700 | 1 | |a Sun, Difei |4 oth | |
| 700 | 1 | |a Li, Liang |4 oth | |
| 700 | 1 | |a Fliegel, Larry |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Alizadeh, H. ELSEVIER |t Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre |d 2015 |g New York, NY [u.a.] |w (DE-627)ELV012763152 |
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10.1016/j.yjmcc.2016.08.014 doi GBVA2016023000003.pica (DE-627)ELV030128382 (ELSEVIER)S0022-2828(16)30314-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 333.7 610 VZ 43.12 bkl 43.13 bkl 44.13 bkl Li, Xiuju verfasserin aut Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail 2016transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. Augustine, Aruna oth Sun, Difei oth Li, Liang oth Fliegel, Larry oth Enthalten in Elsevier Alizadeh, H. ELSEVIER Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre 2015 New York, NY [u.a.] (DE-627)ELV012763152 volume:99 year:2016 pages:65-75 extent:11 https://doi.org/10.1016/j.yjmcc.2016.08.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-GGO 43.12 Umweltchemie VZ 43.13 Umwelttoxikologie VZ 44.13 Medizinische Ökologie VZ AR 99 2016 65-75 11 045F 610 |
| spelling |
10.1016/j.yjmcc.2016.08.014 doi GBVA2016023000003.pica (DE-627)ELV030128382 (ELSEVIER)S0022-2828(16)30314-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 333.7 610 VZ 43.12 bkl 43.13 bkl 44.13 bkl Li, Xiuju verfasserin aut Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail 2016transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. Augustine, Aruna oth Sun, Difei oth Li, Liang oth Fliegel, Larry oth Enthalten in Elsevier Alizadeh, H. ELSEVIER Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre 2015 New York, NY [u.a.] (DE-627)ELV012763152 volume:99 year:2016 pages:65-75 extent:11 https://doi.org/10.1016/j.yjmcc.2016.08.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-GGO 43.12 Umweltchemie VZ 43.13 Umwelttoxikologie VZ 44.13 Medizinische Ökologie VZ AR 99 2016 65-75 11 045F 610 |
| allfields_unstemmed |
10.1016/j.yjmcc.2016.08.014 doi GBVA2016023000003.pica (DE-627)ELV030128382 (ELSEVIER)S0022-2828(16)30314-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 333.7 610 VZ 43.12 bkl 43.13 bkl 44.13 bkl Li, Xiuju verfasserin aut Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail 2016transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. Augustine, Aruna oth Sun, Difei oth Li, Liang oth Fliegel, Larry oth Enthalten in Elsevier Alizadeh, H. ELSEVIER Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre 2015 New York, NY [u.a.] (DE-627)ELV012763152 volume:99 year:2016 pages:65-75 extent:11 https://doi.org/10.1016/j.yjmcc.2016.08.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-GGO 43.12 Umweltchemie VZ 43.13 Umwelttoxikologie VZ 44.13 Medizinische Ökologie VZ AR 99 2016 65-75 11 045F 610 |
| allfieldsGer |
10.1016/j.yjmcc.2016.08.014 doi GBVA2016023000003.pica (DE-627)ELV030128382 (ELSEVIER)S0022-2828(16)30314-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 333.7 610 VZ 43.12 bkl 43.13 bkl 44.13 bkl Li, Xiuju verfasserin aut Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail 2016transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. Augustine, Aruna oth Sun, Difei oth Li, Liang oth Fliegel, Larry oth Enthalten in Elsevier Alizadeh, H. ELSEVIER Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre 2015 New York, NY [u.a.] (DE-627)ELV012763152 volume:99 year:2016 pages:65-75 extent:11 https://doi.org/10.1016/j.yjmcc.2016.08.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-GGO 43.12 Umweltchemie VZ 43.13 Umwelttoxikologie VZ 44.13 Medizinische Ökologie VZ AR 99 2016 65-75 11 045F 610 |
| allfieldsSound |
10.1016/j.yjmcc.2016.08.014 doi GBVA2016023000003.pica (DE-627)ELV030128382 (ELSEVIER)S0022-2828(16)30314-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 333.7 610 VZ 43.12 bkl 43.13 bkl 44.13 bkl Li, Xiuju verfasserin aut Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail 2016transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. Augustine, Aruna oth Sun, Difei oth Li, Liang oth Fliegel, Larry oth Enthalten in Elsevier Alizadeh, H. ELSEVIER Outcome of pregnancy in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors: Short report from a single centre 2015 New York, NY [u.a.] (DE-627)ELV012763152 volume:99 year:2016 pages:65-75 extent:11 https://doi.org/10.1016/j.yjmcc.2016.08.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-GGO 43.12 Umweltchemie VZ 43.13 Umwelttoxikologie VZ 44.13 Medizinische Ökologie VZ AR 99 2016 65-75 11 045F 610 |
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activation of the na+/h+ exchanger in isolated cardiomyocytes through β-raf dependent pathways. role of thr653 of the cytosolic tail |
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Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail |
| abstract |
The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. |
| abstractGer |
The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. |
| abstract_unstemmed |
The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. |
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Activation of the Na+/H+ exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr653 of the cytosolic tail |
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