Requirement of GM2 ganglioside activator for phospholipase D activation

Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12249-53. doi: 10.1073/pnas.95.21.12249.


Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known GM2 ganglioside activator whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2 to GM3 ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, GM2 ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792-815] stimulates ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Enzyme Activation
  • G(M2) Activator Protein
  • Liver / enzymology
  • Molecular Sequence Data
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phospholipase D / chemistry
  • Phospholipase D / metabolism*
  • Protein Kinase C / metabolism
  • Proteins / metabolism*
  • Rats
  • Sequence Homology, Amino Acid


  • G(M2) Activator Protein
  • Phosphatidylinositol 4,5-Diphosphate
  • Proteins
  • Protein Kinase C
  • Phospholipase D