Catalytic Inactivation of Human Phospholipase D2 by a Naturally Occurring Gly901Asp Mutation
Received 1 September 2005; accepted 4 January 2006.
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.
Results and Conclusions
The G→A (Gly901Asp) mutation of the human PLD2 gene was found to result in catalytic inactivation of the encoded protein.
aDepartment of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan
bDepartment of Cell Signaling, Gifu University Graduate School of Medicine, Gifu, Japan
cMolecular Oncology Division, National Cancer Center Research Institute, Tokyo, Japan
dNagoya University School of Health Sciences, Nagoya, Japan
eGifu International Institute of Biotechnology, Kakamigahara, Japan
Address reprint requests to: Yoshiji Yamada, MD, PhD, FAHA, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan
ABSTRACT