Activation of a small GTP-binding protein by nucleoside diphosphate kinase.
Genes that encode nucleoside diphosphate kinases (NDKs) have been implicated as regulators of mammalian tumor metastasis and development in Drosophila melanogaster. However, the cellular pathways through which NDKs function are not known. One potential mechanism of regulation is phosphorylation of guanosine diphosphate (GDP) bound to regulatory guanosine triphosphate (GTP) binding proteins. NDK-catalyzed phosphorylation of bound GDP was investigated for the adenosine diphosphate ribosylation factor (ARF), a 21-kilodalton GTP-binding protein that functions in the protein secretion pathway. Bovine liver NDK, recombinant human NDK, and the protein product of the mouse gene nm23-1, which suppresses the metastatic potential of certain tumor cells, used ARF-GDP as a substrate, thereby allowing rapid and efficient production of activated ARF (ARF-GTP) in the absence of nucleotide exchange. These data are consistent with the proposed function of NDK as an activator of a small GTP-binding protein and provide a mechanism of activation for a regulatory GTP-binding protein that is independent of nucleotide exchange.
Randazzo
P A
PA
Laboratory of Biological Chemistry, National Cancer Institute, Bethesda, MD 20892.
Northup
J K
JK
Kahn
R A
RA
D000818:Animals; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D009701:Nucleoside-Diphosphate Kinase; D019204:GTP-Binding Proteins