A product of the prune locus of Drosophila is similar to mammalian GTPase-activating protein.
The X-linked prune (pn) eye-colour mutation of Drosophila melanogaster has a highly specific, complementary lethal interaction with the conditional dominant Killer of prune (awdK-pn) mutation. Although awdK-pn flies have no apparent phenotype on their own, pn awdK-pn double mutants die as second or third larval instars. The awd locus encodes a nucleoside diphosphate kinase, an enzyme that catalyses the transfer of high-energy phosphate bonds between nucleoside diphosphates and nucleoside triphosphates, which is essential for the normal development of Drosophila. Analysis of the pn locus has suggested that the complementary DNA, TcD37, encodes a putative pn+ product. Here we report the nucleotide sequence of TcD37 and the similarity of its deduced protein product to the catalytic domain of mammalian GTPase-activating proteins (GAPs); GAPs stimulate the GTPase activity of Ras (ref. 6), which are plasma membrane-bound proteins involved in the regulation of cell proliferation and differentiation. These results suggest that the Drosophila TcD37 protein participates in a biochemical pathway similar to that of Ras and GAPs in mammals and yeast. We propose that the interaction between pn and awd is due to a neomorphic mutation that enhances the ability of AwdK-pn nucleoside diphosphate kinase to induce a regulatory GTPase into a GTP-bound 'on' state, whereas Pn modulates the activity of this GTPase either by switching it to a GDP-bound 'off' state or by interfering with its effector function.
Teng
D H
DH
Institute of Molecular Biology, University of Oregon, Eugene 97403.
Engele
C M
CM
Venkatesh
T R
TR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005127:Eye Color / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D005804:Genes, Lethal; D007301:Insect Hormones / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D020703:ras GTPase-Activating Proteins
D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D007301:Insect Hormones; C070996:PN protein, Drosophila; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila; D020558:GTP Phosphohydrolases