Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor

The binding of aldosterone (ALDO) to the mineralocorticoid receptor (MR) induces a conformational change of the protein referred to as 'transformation'. This feature can be evidenced in vivo by the capacity of the MR to interact with chromatin, and in vitro by the ability of the MR to bind...

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Publicado:	1998
Materias:	Mineralocorticoid receptor Protein phosphatases Receptor transformation Tautomycin (rat kidney) acid phosphatase aldosterone alkaline phosphatase levamisole mineralocorticoid receptor phosphoprotein phosphatase tautomycin transcription factor animal tissue article complex formation conformational transition controlled study cytosol enzyme activity enzyme inhibition kidney male nonhuman phosphorylation priority journal protein conformation rat reaction time signal transduction temperature dependence Aldosterone Alkaline Phosphatase Animals Antibiotics, Antifungal Cell Nucleus Cellulose Centrifugation, Density Gradient Chromatography, Ion Exchange Cytoplasm DNA Dose-Response Relationship, Drug Kidney Kinetics Levamisole Male Phosphoprotein Phosphatase Protein Conformation Pyrans Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid Spiro Compounds Temperature
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v144_n1-2_p119_PiwienPilipuk http://hdl.handle.net/20.500.12110/paper_03037207_v144_n1-2_p119_PiwienPilipuk
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_03037207_v144_n1-2_p119_PiwienPilipuk
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spelling	paper:paper_03037207_v144_n1-2_p119_PiwienPilipuk2025-07-30T18:06:43Z Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor Mineralocorticoid receptor Protein phosphatases Receptor transformation Tautomycin (rat kidney) acid phosphatase aldosterone alkaline phosphatase levamisole mineralocorticoid receptor phosphoprotein phosphatase tautomycin transcription factor animal tissue article complex formation conformational transition controlled study cytosol enzyme activity enzyme inhibition kidney male nonhuman phosphorylation priority journal protein conformation rat reaction time signal transduction temperature dependence Aldosterone Alkaline Phosphatase Animals Antibiotics, Antifungal Cell Nucleus Cellulose Centrifugation, Density Gradient Chromatography, Ion Exchange Cytoplasm DNA Dose-Response Relationship, Drug Kidney Kinetics Levamisole Male Phosphoprotein Phosphatase Protein Conformation Pyrans Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid Spiro Compounds Temperature The binding of aldosterone (ALDO) to the mineralocorticoid receptor (MR) induces a conformational change of the protein referred to as 'transformation'. This feature can be evidenced in vivo by the capacity of the MR to interact with chromatin, and in vitro by the ability of the MR to bind to DNA strands or to shift the sedimentation coefficient (S) to lower values. The transformation process allows MR to work as a transcription factor after interacting with specific sequences of DNA. The signal transduction pathway for the MR transformation remains unknown. As a first step towards elucidating the mechanism of steroid-dependent MR transformation, we asked if the MR-signaling pathway is affected by the phosphorylation status of the MR-heterocomplex, and how that pathway may be regulated. Incubation of preformed [3H]ALDO-MR complex with bovine intestinal alkaline phosphatase led to an increase in the rate of MR-transformation (measured as 9.4-5.4S shift). This alkaline phosphatase-dependent MR transformation was inhibited by the specific alkaline phosphatase-type inhibitor levamisole, and was not evident in incubations performed with acid phosphatases. A direct correlation between the DNA-cellulose binding capacity of the [3H]ALDO-MR complex and the percentage of transformed 5.4S MR form was also observed. When rat kidney cytosol was incubated in the absence of both exogenous phosphatase and stabilizing agents (such as molybdate or vanadate), MR transformation also took place, in a time- and temperature-dependent process. In contrast with the inhibitory effect observed upon alkaline phosphatase-promoted transformation, levamisole was unable to inhibit the endogenous transforming activity of MR, suggesting that an endogenous phosphatase other than those which belong to the alkaline-type may be responsible for that transformation. Tautomycin, a polyketide produced by the soil bacteria Streptomyces which inhibits serine/threonine phosphatases of the PP1/PP2A subgroup, was able to inhibit the endogenous phosphatase activity in a concentration-dependent form (K(i(app))=7.35 nM). These results support the idea that the endogenous renal activity involved in the regulation of rat kidney MR transformation may be a protein phosphatase which belongs to the PP1/PP2A subgroup. Copyright (C) 1998 Elsevier Science Ireland Ltd. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v144_n1-2_p119_PiwienPilipuk http://hdl.handle.net/20.500.12110/paper_03037207_v144_n1-2_p119_PiwienPilipuk
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Mineralocorticoid receptor Protein phosphatases Receptor transformation Tautomycin (rat kidney) acid phosphatase aldosterone alkaline phosphatase levamisole mineralocorticoid receptor phosphoprotein phosphatase tautomycin transcription factor animal tissue article complex formation conformational transition controlled study cytosol enzyme activity enzyme inhibition kidney male nonhuman phosphorylation priority journal protein conformation rat reaction time signal transduction temperature dependence Aldosterone Alkaline Phosphatase Animals Antibiotics, Antifungal Cell Nucleus Cellulose Centrifugation, Density Gradient Chromatography, Ion Exchange Cytoplasm DNA Dose-Response Relationship, Drug Kidney Kinetics Levamisole Male Phosphoprotein Phosphatase Protein Conformation Pyrans Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid Spiro Compounds Temperature
spellingShingle	Mineralocorticoid receptor Protein phosphatases Receptor transformation Tautomycin (rat kidney) acid phosphatase aldosterone alkaline phosphatase levamisole mineralocorticoid receptor phosphoprotein phosphatase tautomycin transcription factor animal tissue article complex formation conformational transition controlled study cytosol enzyme activity enzyme inhibition kidney male nonhuman phosphorylation priority journal protein conformation rat reaction time signal transduction temperature dependence Aldosterone Alkaline Phosphatase Animals Antibiotics, Antifungal Cell Nucleus Cellulose Centrifugation, Density Gradient Chromatography, Ion Exchange Cytoplasm DNA Dose-Response Relationship, Drug Kidney Kinetics Levamisole Male Phosphoprotein Phosphatase Protein Conformation Pyrans Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid Spiro Compounds Temperature Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
topic_facet	Mineralocorticoid receptor Protein phosphatases Receptor transformation Tautomycin (rat kidney) acid phosphatase aldosterone alkaline phosphatase levamisole mineralocorticoid receptor phosphoprotein phosphatase tautomycin transcription factor animal tissue article complex formation conformational transition controlled study cytosol enzyme activity enzyme inhibition kidney male nonhuman phosphorylation priority journal protein conformation rat reaction time signal transduction temperature dependence Aldosterone Alkaline Phosphatase Animals Antibiotics, Antifungal Cell Nucleus Cellulose Centrifugation, Density Gradient Chromatography, Ion Exchange Cytoplasm DNA Dose-Response Relationship, Drug Kidney Kinetics Levamisole Male Phosphoprotein Phosphatase Protein Conformation Pyrans Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid Spiro Compounds Temperature
description	The binding of aldosterone (ALDO) to the mineralocorticoid receptor (MR) induces a conformational change of the protein referred to as 'transformation'. This feature can be evidenced in vivo by the capacity of the MR to interact with chromatin, and in vitro by the ability of the MR to bind to DNA strands or to shift the sedimentation coefficient (S) to lower values. The transformation process allows MR to work as a transcription factor after interacting with specific sequences of DNA. The signal transduction pathway for the MR transformation remains unknown. As a first step towards elucidating the mechanism of steroid-dependent MR transformation, we asked if the MR-signaling pathway is affected by the phosphorylation status of the MR-heterocomplex, and how that pathway may be regulated. Incubation of preformed [3H]ALDO-MR complex with bovine intestinal alkaline phosphatase led to an increase in the rate of MR-transformation (measured as 9.4-5.4S shift). This alkaline phosphatase-dependent MR transformation was inhibited by the specific alkaline phosphatase-type inhibitor levamisole, and was not evident in incubations performed with acid phosphatases. A direct correlation between the DNA-cellulose binding capacity of the [3H]ALDO-MR complex and the percentage of transformed 5.4S MR form was also observed. When rat kidney cytosol was incubated in the absence of both exogenous phosphatase and stabilizing agents (such as molybdate or vanadate), MR transformation also took place, in a time- and temperature-dependent process. In contrast with the inhibitory effect observed upon alkaline phosphatase-promoted transformation, levamisole was unable to inhibit the endogenous transforming activity of MR, suggesting that an endogenous phosphatase other than those which belong to the alkaline-type may be responsible for that transformation. Tautomycin, a polyketide produced by the soil bacteria Streptomyces which inhibits serine/threonine phosphatases of the PP1/PP2A subgroup, was able to inhibit the endogenous phosphatase activity in a concentration-dependent form (K(i(app))=7.35 nM). These results support the idea that the endogenous renal activity involved in the regulation of rat kidney MR transformation may be a protein phosphatase which belongs to the PP1/PP2A subgroup. Copyright (C) 1998 Elsevier Science Ireland Ltd.
title	Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
title_short	Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
title_full	Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
title_fullStr	Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
title_full_unstemmed	Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
title_sort	tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor
publishDate	1998
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v144_n1-2_p119_PiwienPilipuk http://hdl.handle.net/20.500.12110/paper_03037207_v144_n1-2_p119_PiwienPilipuk
_version_	1840327502732460032

Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor

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