Catalytic inactivation of human phospholipase D2 by a naturally occurring Gly901Asp mutation.
BACKGROUND
We previously showed that the 1814C-->T (Thr577Ile) polymorphism of the human phospholipase D2 (PLD2) gene is associated with the prevalence of colorectal cancer, with the T allele representing a risk factor for this condition. However, we failed to detect a difference in PLD activity of cell lysates or membrane fractions between cells transfected with cDNAs encoding the Thr577 or Ile577 variants of PLD2. In the present study, we have examined the possible functional relevance of other naturally occurring polymorphisms (or mutations) of the human PLD2 gene that result in amino acid substitutions.


METHODS
Human embryonic kidney cells were transfected with expression vectors for each PLD2 variant and assayed for enzyme activity in vitro and in vivo.


CONCLUSIONS
The G-->A (Gly901Asp) mutation of the human PLD2 gene was found to result in catalytic inactivation of the encoded protein.
Yamada
Yoshiji
Y
Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan. yamada@gene.mie-u.ac.jp
Banno
Yoshiko
Y
Yoshida
Hitoshi
H
Kikuchi
Ryosuke
R
Akao
Yukihiro
Y
Murate
Takashi
T
Nozawa
Yoshinori
Y
D000483:Alleles; D001224:Aspartic Acid / Q000378:metabolism*; D002460:Cell Line; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide
D001224:Aspartic Acid; C105606:phospholipase D2; D010739:Phospholipase D; D005998:Glycine