Molecular Cloning of Mevalonate Kinase and Regulation of its mRNA Levels in Rat Liver
Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA libra...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1990-04, Vol.87 (8), p.2872-2876 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Tanaka, Richard D. Lee, Lynn Y. Schafer, Beverly L. Kratunis, Valerie J. Mohler, William A. Robinson, Gordon W. Mosley, Stephen T. |
| description | Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was ≈ 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA. |
| doi_str_mv | 10.1073/pnas.87.8.2872 |
| format | Article |
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To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was ≈ 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.87.8.2872</identifier><identifier>PMID: 2158094</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Animals ; Base Sequence ; Cholesterols ; Cloning, Molecular ; Complementary DNA ; DNA - genetics ; DNA - isolation & purification ; Enzymes ; Female ; Gene Expression ; Gene expression regulation ; Liver ; Liver - enzymology ; Messenger RNA ; mevalonate kinase ; Molecular Sequence Data ; Nucleotides ; Phosphotransferases (Alcohol Group Acceptor) ; Phosphotransferases - genetics ; Protein Conformation ; Rats ; Rats, Inbred Strains ; RNA, Messenger - genetics ; Saccharomyces cerevisiae - genetics ; Sequence Homology, Nucleic Acid ; Sequencing ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1990-04, Vol.87 (8), p.2872-2876</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4032-14dc0bd2f5e4772b4f7ed1ed770228859a988dacbf23f99f789dc2c5343a53173</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/87/8.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2354060$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2354060$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2158094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanaka, Richard D.</creatorcontrib><creatorcontrib>Lee, Lynn Y.</creatorcontrib><creatorcontrib>Schafer, Beverly L.</creatorcontrib><creatorcontrib>Kratunis, Valerie J.</creatorcontrib><creatorcontrib>Mohler, William A.</creatorcontrib><creatorcontrib>Robinson, Gordon W.</creatorcontrib><creatorcontrib>Mosley, Stephen T.</creatorcontrib><title>Molecular Cloning of Mevalonate Kinase and Regulation of its mRNA Levels in Rat Liver</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was ≈ 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Cholesterols</subject><subject>Cloning, Molecular</subject><subject>Complementary DNA</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene expression regulation</subject><subject>Liver</subject><subject>Liver - enzymology</subject><subject>Messenger RNA</subject><subject>mevalonate kinase</subject><subject>Molecular Sequence Data</subject><subject>Nucleotides</subject><subject>Phosphotransferases (Alcohol Group Acceptor)</subject><subject>Phosphotransferases - genetics</subject><subject>Protein Conformation</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>RNA, Messenger - genetics</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Sequencing</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd2LEzEUxYO4rHX11SeFPPk2s_lsEvBlKX5hV6G4zyHN3NQs6aROZor-987QWrsg7NMlnN-554aD0CtKakoUv961rtRa1bpmWrEnaEaJodVcGPIUzQhhqtKCiWfoeSn3hBAjNblEl4yO04gZurvNCfyQXIcXKbex3eAc8C3s3fhyPeAvcQwA7NoGr2Azgn3M7cTEvuDt6usNXsIeUsGxxSvX42XcQ_cCXQSXCrw8zit09-H998Wnavnt4-fFzbLygnBWUdF4sm5YkCCUYmsRFDQUGqUIY1pL44zWjfPrwHgwJihtGs-85II7yaniV-jdYe9uWG-h8dD2nUt218Wt637b7KJ9qLTxh93kvZVcGTna3x7tXf45QOntNhYPKbkW8lCsMoqpOaGPglRKbcZ7R7A-gL7LpXQQTrdQYqe-7NSX1cpqO_U1Gt6c_-CEHws6S558f9WT34YhpR5-9WeL_guO-uuDfl_63P3L4VKQOeF_ANPLsqE</recordid><startdate>19900401</startdate><enddate>19900401</enddate><creator>Tanaka, Richard D.</creator><creator>Lee, Lynn Y.</creator><creator>Schafer, Beverly L.</creator><creator>Kratunis, Valerie J.</creator><creator>Mohler, William A.</creator><creator>Robinson, Gordon W.</creator><creator>Mosley, Stephen T.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19900401</creationdate><title>Molecular Cloning of Mevalonate Kinase and Regulation of its mRNA Levels in Rat Liver</title><author>Tanaka, Richard D. ; Lee, Lynn Y. ; Schafer, Beverly L. ; Kratunis, Valerie J. ; Mohler, William A. ; Robinson, Gordon W. ; Mosley, Stephen T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4032-14dc0bd2f5e4772b4f7ed1ed770228859a988dacbf23f99f789dc2c5343a53173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Cholesterols</topic><topic>Cloning, Molecular</topic><topic>Complementary DNA</topic><topic>DNA - genetics</topic><topic>DNA - isolation & purification</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene expression regulation</topic><topic>Liver</topic><topic>Liver - enzymology</topic><topic>Messenger RNA</topic><topic>mevalonate kinase</topic><topic>Molecular Sequence Data</topic><topic>Nucleotides</topic><topic>Phosphotransferases (Alcohol Group Acceptor)</topic><topic>Phosphotransferases - genetics</topic><topic>Protein Conformation</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>RNA, Messenger - genetics</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Sequencing</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanaka, Richard D.</creatorcontrib><creatorcontrib>Lee, Lynn Y.</creatorcontrib><creatorcontrib>Schafer, Beverly L.</creatorcontrib><creatorcontrib>Kratunis, Valerie J.</creatorcontrib><creatorcontrib>Mohler, William A.</creatorcontrib><creatorcontrib>Robinson, Gordon W.</creatorcontrib><creatorcontrib>Mosley, Stephen T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanaka, Richard D.</au><au>Lee, Lynn Y.</au><au>Schafer, Beverly L.</au><au>Kratunis, Valerie J.</au><au>Mohler, William A.</au><au>Robinson, Gordon W.</au><au>Mosley, Stephen T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Cloning of Mevalonate Kinase and Regulation of its mRNA Levels in Rat Liver</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1990-04-01</date><risdate>1990</risdate><volume>87</volume><issue>8</issue><spage>2872</spage><epage>2876</epage><pages>2872-2876</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was ≈ 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>2158094</pmid><doi>10.1073/pnas.87.8.2872</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1990-04, Vol.87 (8), p.2872-2876 |
| issn | 0027-8424 1091-6490 |
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| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Amino acids Animals Base Sequence Cholesterols Cloning, Molecular Complementary DNA DNA - genetics DNA - isolation & purification Enzymes Female Gene Expression Gene expression regulation Liver Liver - enzymology Messenger RNA mevalonate kinase Molecular Sequence Data Nucleotides Phosphotransferases (Alcohol Group Acceptor) Phosphotransferases - genetics Protein Conformation Rats Rats, Inbred Strains RNA, Messenger - genetics Saccharomyces cerevisiae - genetics Sequence Homology, Nucleic Acid Sequencing Yeasts |
| title | Molecular Cloning of Mevalonate Kinase and Regulation of its mRNA Levels in Rat Liver |
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