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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
1997-7-14
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pubmed:abstractText |
The phosphorylase phosphatase activity of protein phosphatase 1 (PP1) catalytic subunit from freshly purified rabbit skeletal muscle was inhibited by MnCl2. Prolonged storage or inhibition by nonspecific phosphatase inhibitors ATP, sodium pyrophosphate, and NaF converted the muscle PP1 to a form that required Mn2+ for enzyme activity. Recombinant PP1 catalytic subunit expressed in Escherichia coli was also a Mn2+-dependent enzyme. While native PP1 was inhibited by the phosphoprotein inhibitor I (I-1), with an IC50 of 1 nM, 40-50-fold higher concentrations of I-1 were required to inhibit the Mn2+-dependent PP1 enzymes. Conversion to the Mn2+-dependent state was accompanied by a 20-fold increase in PP1's ability to dephosphorylate and inactivate I-1. Inhibition by thiophosphorylated I-1 established that dephosphorylation does not play a significant role in I-1's reduced potency as an inhibitor of Mn2+-dependent PP1. The Mn2+-dependent PP1 enzymes were poorly inhibited by N-terminal phosphopeptides of I-1, indicating their impaired interaction with the I-1 functional domain. Mutation of a residue conserved in I-1 and DARPP-32, a structurally related PP1 inhibitor, preferentially attenuated I-1's activity as an inhibitor of Mn2+-dependent PP1. These data showed that, in addition to changes in its catalytic properties, Mn2+-dependent PP1 was modified in its interaction with I-1 at a site that was distinct from its catalytic domain. Our studies suggest that conversion to a Mn2+-dependent state alters multiple structural elements in PP1 catalytic subunit that together define its regulation by I-1.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Endoribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Manganese,
http://linkedlifedata.com/resource/pubmed/chemical/Manganese Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/PPP1R8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/manganese chloride,
http://linkedlifedata.com/resource/pubmed/chemical/protein phosphatase inhibitor-1
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6986-92
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9188695-Amino Acid Sequence,
pubmed-meshheading:9188695-Animals,
pubmed-meshheading:9188695-Carrier Proteins,
pubmed-meshheading:9188695-Catalysis,
pubmed-meshheading:9188695-Chlorides,
pubmed-meshheading:9188695-Endoribonucleases,
pubmed-meshheading:9188695-Enzyme Inhibitors,
pubmed-meshheading:9188695-Humans,
pubmed-meshheading:9188695-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:9188695-Manganese,
pubmed-meshheading:9188695-Manganese Compounds,
pubmed-meshheading:9188695-Models, Molecular,
pubmed-meshheading:9188695-Molecular Sequence Data,
pubmed-meshheading:9188695-Mutagenesis, Site-Directed,
pubmed-meshheading:9188695-Phosphoprotein Phosphatases,
pubmed-meshheading:9188695-Phosphorylation,
pubmed-meshheading:9188695-Protein Conformation,
pubmed-meshheading:9188695-Protein Phosphatase 1,
pubmed-meshheading:9188695-Proteins,
pubmed-meshheading:9188695-RNA-Binding Proteins,
pubmed-meshheading:9188695-Rabbits,
pubmed-meshheading:9188695-Substrate Specificity
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pubmed:year |
1997
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pubmed:articleTitle |
Conversion of protein phosphatase 1 catalytic subunit to a Mn(2+)-dependent enzyme impairs its regulation by inhibitor 1.
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pubmed:affiliation |
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710-0001, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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