Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence

Ken L. Chambliss, Clive A. Slaughter, Rupert Schreiner, Georg F. Hoffmann, K. Michael Gibson

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Two overlapping cDNAs which encode human liver phosphomevalonate kinase (PMKase) were isolated. The human PMKase cDNAs predict a 191-amino acid protein with a molecular weight of 21,862, consistent with previous reports for mammalian PMKase (M(r) = 21,00022,500). Further verification of the clones was obtained by expression of PMKase activity in bacteria using a composite 1024-base pair cDNA clone. Northern blot analysis of several human tissues revealed a doublet of transcripts at approximately 1 kilobase (kb) in heart, liver, skeletal muscle, kidney, and pancreas and lower but detectable transcript levels in brain, placenta, and lung. Analysis of transcripts from human lymphoblasts subcultured in lipid-depleted sera (LDS) and LDS supplemented with lovastatin indicated that PMKase gene expression is subject to regulation by sterol at the level of transcription. Southern blotting indicated that PMKase is a single copy gene covering less than 15 kb in the human genome. The human PMKase amino acid sequence contains a consensus peroxisomal targeting sequence (PTS-1), Ser-Arg-Leu, at the C terminus of the protein. This is the first report of a cholesterol biosynthetic protein which contains a consensus PTS-1, providing further evidence for the concept that early cholesterol and nonsterol isoprenoid biosynthesis may occur in the peroxisome.

Original languageEnglish (US)
Pages (from-to)17330-17334
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number29
DOIs
StatePublished - Aug 5 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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