Requirement of GM2 ganglioside activator for phospholipase D activation.
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.
Department of Biochemistry, Kobe University School of Medicine, Kobe 650-0017, Japan.
S
S
Nakamura
T
T
Akisue
H
H
Jinnai
T
T
Hitomi
S
S
Sarkar
N
N
Miwa
T
T
Okada
K
K
Yoshida
S
S
Kuroda
U
U
Kikkawa
Y
Y
Nishizuka
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D049289:G(M2) Activator Protein; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010739:Phospholipase D / Q000737:chemistry / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid
D049289:G(M2) Activator Protein; D019269:Phosphatidylinositol 4,5-Diphosphate; D011506:Proteins; D011493:Protein Kinase C; D010739:Phospholipase D