Requirement of GM2Ganglioside Activator for Phospholipase D Activation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 21; pp. 12249 - 12253
• Main Authors: Nakamura, Shun-Ichi, Akisue, Toshihiro, Jinnai, Hitoshi, Hitomi, Tomohiro, Sarkar, Sukumar, Miwa, Noriko, Okada, Taro, Yoshida, Kimihisa, Kuroda, Shun'ichi, Kikkawa, Ushio, Nishizuka, Yasutomi
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of the United States of America 13-10-1998
• Subjects: Amino acids; Biochemistry; Enzymes; Gangliosides; Kidneys; Lipids; Phosphatidylinositols; Quaternary ammonium compounds; Research facilities; Sulfates
• ISSN: 0027-8424; 1091-6490

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 GM2ganglioside activator whose deficiency results in the AB-variant of GM2gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2to GM3ganglioside that is catalyzed by β -hexosaminidase A. Inversely, GM2ganglioside 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.