Human phosphatidylinositol 4-kinase isoform PI4K92. Expression of the recombinant enzyme and determination of multiple phosphorylation sites

Eur J Biochem. 2001 Apr;268(7):2099-106. doi: 10.1046/j.1432-1327.2001.02089.x.

Abstract

Human phosphatidylinositol 4-kinase, isoform PI4K92, was expressed as His6 tagged protein in Sf9 cells reaching a level of approximately 5% of cellular protein. The enzyme can be purified nearly to homogeneity in a single step by absorption/desorption on Ni/nitriloacetic acid agarose magnetic beads. High Km values in the millimolar range for ATP and PtdIns as well as only a moderate inhibition by adenosine and a sensitivity to Wortmannin (IC50 approximately 300 nM) characterize the enzyme as a type 3 PI4K. The enzyme produces PtdIns4P as product. The isolated enzyme is a phosphoprotein, additionally phosphate is incorporated by incubation with ATP/Mg or ATP/Mn. Phosphorylation sites were mapped by MALDI-MS and LC-MS/MS at the following positions: S258, T263, S266, S277, S294, T423, S496, T504. Accordingly, a stretch of 81 amino acids between the common and the C-terminal catalytic domain was designated phosphorylation domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / biosynthesis*
  • 1-Phosphatidylinositol 4-Kinase / isolation & purification
  • Adenosine / metabolism
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Catalytic Domain
  • Cell Line
  • Chromatography, Liquid
  • Histidine / metabolism
  • Humans
  • Isoenzymes / biosynthesis*
  • Isoenzymes / isolation & purification
  • Kinetics
  • Magnetics
  • Mass Spectrometry
  • Molecular Sequence Data
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphorylation
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spodoptera

Substances

  • Isoenzymes
  • Phosphatidylinositol Phosphates
  • Recombinant Proteins
  • phosphatidylinositol 4-phosphate
  • Histidine
  • Adenosine Triphosphate
  • 1-Phosphatidylinositol 4-Kinase
  • Adenosine

Associated data

  • GENBANK/U81802
  • GENBANK/X83368