title: Enzymological analysis of the tumor suppressor A-C1 reveals a novel group of phospholipid-metabolizing enzymes.
abstract: A-C1 protein is the product of a tumor suppressor gene negatively regulating the oncogene Ras and belongs to the HRASLS (HRAS-like suppressor) subfamily. We recently found that four members of this subfamily expressed in human tissues function as phospholipid-metabolizing enzymes. Here we examined a possible enzyme activity of A-C1. The homogenates of COS-7 cells overexpressing recombinant A-C1s from human, mouse, and rat showed a phospholipase A½ (PLA½) activity toward phosphatidylcholine (PC). This finding was confirmed with the purified A-C1. The activity was Ca²⁺ independent, and dithiothreitol and Nonidet P-40 were indispensable for full activity. Phosphatidylethanolamine (PE) was also a substrate and the phospholipase A₁ (PLA₁) activity was dominant over the PLA₂ activity. Furthermore, the protein exhibited acyltransferase activities transferring an acyl group of PCs to the amino group of PEs and the hydroxyl group of lyso PCs. As for tissue distribution in human, mouse, and rat, A-C1 mRNA was abundantly expressed in testis, skeletal muscle, brain, and heart. These results demonstrate that A-C1 is a novel phospholipid-metabolizing enzyme. Moreover, the fact that all five members of the HRASLS subfamily, including A-C1, show similar catalytic properties strongly suggests that these proteins constitute a new class of enzymes showing PLA½ and acyltransferase activities.
authors: Department of Biochemistry, Kagawa University School of Medicine, Miki, Kagawa 761-0793, Japan.
authors: Naoki
authors: N
authors: Shinohara
authors: Toru
authors: T
authors: Uyama
authors: Xing-Hua
authors: XH
authors: Jin
authors: Kazuhito
authors: K
authors: Tsuboi
authors: Takeharu
authors: T
authors: Tonai
authors: Hitoshi
authors: H
authors: Houchi
authors: Natsuo
authors: N
authors: Ueda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D019556:COS Cells; D057075:Enzyme Assays; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010741:Phospholipases A; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D010743:Phospholipids; D011506:Proteins; C433809:PLAAT1 protein, human; D010741:Phospholipases A