Binding of elongation factor eEF1A2 to phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and phosphatidylinositol 4-phosphate generation.
Eukaryotic protein translation elongation factor 1 alpha 2 (eEF1A2) is an oncogene that transforms mammalian cell lines and increases their tumorigenicity in nude mice. Increased expression of eEF1A2 occurs during the development of breast, ovarian, and lung cancer. Here, we report that eEF1A2 directly binds to and activates phosphatidylinositol 4-kinase III beta (PI4KIIIbeta), an enzyme that converts phosphatidylinositol to phosphatidylinositol 4-phosphate. Purified recombinant eEF1A2 increases PI4KIIIbeta lipid kinase activity in vitro, and expression of eEF1A2 in rat and human cells is sufficient to increase overall cellular phosphatidylinositol 4-kinase activity and intracellular phosphatidylinositol 4-phosphate abundance. siRNA-mediated reduction in eEF1A2 expression concomitantly reduces phosphatidylinositol 4-kinase activity. This identifies a physical and functional relationship between eEF1A2 and PI4KIIIbeta.
Jeganathan
Sujeeve
S
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Lee
Jonathan M
JM
D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D015778:Minor Histocompatibility Antigens; D020648:Peptide Elongation Factor 1 / Q000737:chemistry*; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry*; D010770:Phosphotransferases / Q000737:chemistry; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats
C503234:EEF1A2 protein, human; D008055:Lipids; D015778:Minor Histocompatibility Antigens; D020648:Peptide Elongation Factor 1; D018129:Phosphatidylinositol Phosphates; D034741:RNA, Small Interfering; C037178:phosphatidylinositol 4-phosphate; D005982:Glutathione Transferase; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase