Open AccessRequirement of G M2 ganglioside activator for phospholipase D activation
Author(s) -
Shunichi Nakamura,
Toshihiro Akisue,
Hitoshi Jinnai,
Tomohiro Hitomi,
Sukumar Sarkar,
Noriko Miwa,
Taro Okada,
Kohsuke Yoshida,
Shinya Kuroda,
Ushio Kikkawa,
Yasutomi Nishizuka
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.21.12249
Subject(s) - activator (genetics) , ganglioside , biochemistry , phospholipase c , enzyme activator , enzyme , adp ribosylation factor , hexosaminidase , chemistry , biology , receptor , cell , golgi apparatus
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 β-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.