The chaperone-like properties of mammalian inhibitor-2 are conserved in a Drosophila homologue

Biochemistry. 1999 Dec 7;38(49):16276-82. doi: 10.1021/bi9917028.

Abstract

Phosphatase inhibitor-2 (I-2) is a mammalian phosphoprotein that binds to the catalytic subunit of type 1 serine/threonine phosphoprotein phosphatase (PP1c) and inhibits its activity in vitro. Recombinant PP1c differs from native PP1c in several biochemical criteria, including the requirement for Mn(2+), sensitivity to vanadate, and p-nitrophenyl phosphate (pNPP) phosphatase activity. I-2 can convert recombinant PP1c into a native-like activity in vitro. It has therefore been suggested that I-2 may act as a molecular chaperone for PP1 in vivo. We have identified a Drosophila homologue (I-2Dm) in a two-hybrid screen for PP1c-binding proteins. The sequence of I-2Dm is 35% identical with that of I-2, whereas the catalytic subunits themselves are >85% identical in flies and humans; however, we show that many biochemical properties of I-2 are conserved. Like I-2, I-2Dm can convert recombinant PP1c to a native-like activity. This strongly suggests that this ability is an essential, conserved role of I-2 and I-2Dm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Catalysis / drug effects
  • Conserved Sequence*
  • DNA, Complementary / isolation & purification
  • Drosophila melanogaster / chemistry*
  • Drosophila melanogaster / genetics
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Hot Temperature
  • Humans
  • Insect Proteins / biosynthesis
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Insect Proteins / pharmacology
  • Molecular Chaperones / chemistry*
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Biosynthesis
  • Protein Phosphatase 1
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / pharmacology
  • Rabbits
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Sequence Analysis
  • Sequence Homology, Amino Acid*

Substances

  • DNA, Complementary
  • Enzyme Inhibitors
  • Insect Proteins
  • Molecular Chaperones
  • Proteins
  • Recombinant Proteins
  • protein phosphatase inhibitor-2
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1

Associated data

  • GENBANK/AJ249461
  • GENBANK/AJ249462