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awd  -  abnormal wing discs

Drosophila melanogaster

Synonyms: 1084/08, Abnormal wing disks protein, Awd, BcDNA:GM19775, BcDNA:RH27794, ...
 
 
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Disease relevance of awd

 

High impact information on awd

  • Neuroblasts in Drosophila larvae homozygous for a null mutation in the awd gene are arrested in metaphase, indicating that microtubule-associated Awd/NDP kinase plays a critical role in spindle microtubule polymerization [1].
  • Consistent with this, Btl-GFP chimera expressed from a cognate btl promoter-driven system accumulate at high levels on tracheal cell membrane of awd mutants as well as in awd RNA duplex-treated cultured cells [5].
  • Using Drosophila tracheal system as a genetic model, we examined the function of the Drosophila homolog of nm23, the awd gene, in cell migration [5].
  • In individuals of the genotype pn; awdK-pn/awd+ the awd mRNA is present at normal levels but the awd polypeptide fails to accumulate [6].
  • The third-chromosome mutation Killer of prune (K-pn) causes no phenotype by itself, but causes lethality in individuals homozygous for the nonlethal X-chromosome mutation prune (pn) [6].
 

Chemical compound and disease context of awd

  • Nm23-H1(S120G), found in advanced human neuroblastomas, exhibited deficient activity in several histidine-dependent protein phosphotransfer reactions, including histidine autophosphorylation, downstream phosphorylation on serines, and slightly decreased histidine protein kinase activity; significant NDPK activity was observed [7].
 

Biological context of awd

  • We show that loss of Drosophila awd results in dysregulated tracheal cell motility [5].
  • Nucleoside diphosphate kinase (NDK), an enzyme encoded by the Drosophila abnormal wing discs (awd) or human nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates [8].
  • This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo [8].
  • We recovered mutant strains at the high rate of approximately 4.8 mutations/kb for every 1000 mutagenized chromosomes from a screen for new mutations in the Drosophila awd gene [9].
  • Drosophila NDP kinase is the product of the abnormal wing disc (awd) developmental gene, a point mutation in which can produce the killer of prune (K-pn) conditional lethal phenotype [10].
 

Anatomical context of awd

 

Associations of awd with chemical compounds

 

Other interactions of awd

 

Analytical, diagnostic and therapeutic context of awd

References

  1. A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase. Biggs, J., Hersperger, E., Steeg, P.S., Liotta, L.A., Shearn, A. Cell (1990) [Pubmed]
  2. The expression of the Drosophila awd gene during normal development and in neoplastic brain tumors caused by lgl mutations. Timmons, L., Hersperger, E., Woodhouse, E., Xu, J., Liu, L.Z., Shearn, A. Dev. Biol. (1993) [Pubmed]
  3. The enzymatic activity of Drosophila AWD/NDP kinase is necessary but not sufficient for its biological function. Xu, J., Liu, L.Z., Deng, X.F., Timmons, L., Hersperger, E., Steeg, P.S., Veron, M., Shearn, A. Dev. Biol. (1996) [Pubmed]
  4. The amino acid sequence of nucleoside diphosphate kinase I from spinach leaves, as deduced from the cDNA sequence. Nomura, T., Yatsunami, K., Honda, A., Sugimoto, Y., Fukui, T., Zhang, J., Yamamoto, J., Ichikawa, A. Arch. Biochem. Biophys. (1992) [Pubmed]
  5. Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Dammai, V., Adryan, B., Lavenburg, K.R., Hsu, T. Genes Dev. (2003) [Pubmed]
  6. Analysis of the lethal interaction between the prune and Killer of prune mutations of Drosophila. Biggs, J., Tripoulas, N., Hersperger, E., Dearolf, C., Shearn, A. Genes Dev. (1988) [Pubmed]
  7. Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro. Freije, J.M., Blay, P., MacDonald, N.J., Manrow, R.E., Steeg, P.S. J. Biol. Chem. (1997) [Pubmed]
  8. Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Krishnan, K.S., Rikhy, R., Rao, S., Shivalkar, M., Mosko, M., Narayanan, R., Etter, P., Estes, P.S., Ramaswami, M. Neuron (2001) [Pubmed]
  9. Targeted recovery of mutations in Drosophila. Bentley, A., MacLennan, B., Calvo, J., Dearolf, C.R. Genetics (2000) [Pubmed]
  10. Crystal structure of the Awd nucleotide diphosphate kinase from Drosophila. Chiadmi, M., Moréra, S., Lascu, I., Dumas, C., Le Bras, G., Véron, M., Janin, J. Structure (1993) [Pubmed]
  11. Molecular consequences of awdb3, a cell-autonomous lethal mutation of Drosophila induced by hybrid dysgenesis. Dearolf, C.R., Tripoulas, N., Biggs, J., Shearn, A. Dev. Biol. (1988) [Pubmed]
  12. The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase. Milon, L., Meyer, P., Chiadmi, M., Munier, A., Johansson, M., Karlsson, A., Lascu, I., Capeau, J., Janin, J., Lacombe, M.L. J. Biol. Chem. (2000) [Pubmed]
  13. A cromoglycate binding protein from rat mast cells of a leukemia line is a nucleoside diphosphate kinase. Hemmerich, S., Yarden, Y., Pecht, I. Biochemistry (1992) [Pubmed]
  14. A novel serine/threonine-specific protein phosphotransferase activity of Nm23/nucleoside-diphosphate kinase. Engel, M., Véron, M., Theisinger, B., Lacombe, M.L., Seib, T., Dooley, S., Welter, C. Eur. J. Biochem. (1995) [Pubmed]
  15. A Pro/Ser substitution in nucleoside diphosphate kinase of Drosophila melanogaster (mutation killer of prune) affects stability but not catalytic efficiency of the enzyme. Lascu, I., Chaffotte, A., Limbourg-Bouchon, B., Véron, M. J. Biol. Chem. (1992) [Pubmed]
  16. Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray structures of the phosphohistidine intermediate of the enzymes from Drosophila and Dictyostelium. Moréra, S., Chiadmi, M., LeBras, G., Lascu, I., Janin, J. Biochemistry (1995) [Pubmed]
  17. Post-translational processing of Drosophila nucleoside diphosphate kinase. Stenberg, L.M., Stenflo, J., Holmgren, P., Brown, M.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Molecular characterization of Ciona sperm outer arm dynein reveals multiple components related to outer arm docking complex protein 2. Hozumi, A., Satouh, Y., Makino, Y., Toda, T., Ide, H., Ogawa, K., King, S.M., Inaba, K. Cell Motil. Cytoskeleton (2006) [Pubmed]
  19. The lethal prune/Killer-of-prune interaction of Drosophila causes a syndrome resembling human neurofibromatosis (NF1). Hackstein, J.H. Eur. J. Cell Biol. (1992) [Pubmed]
  20. Purification and characterization of nucleoside diphosphate kinase from the brain of Bombyx mori. Uno, T., Ueno, M., Kikuchi, M., Aizono, Y. Arch. Insect Biochem. Physiol. (2002) [Pubmed]
  21. Nucleoside diphosphate kinase. Investigation of the intersubunit contacts by site-directed mutagenesis and crystallography. Karlsson, A., Mesnildrey, S., Xu, Y., Moréra, S., Janin, J., Véron, M. J. Biol. Chem. (1996) [Pubmed]
  22. Crystallization and preliminary X-ray diffraction studies of nucleoside diphosphate kinase from Dictyostelium discoideum. Dumas, C., Lebras, G., Wallet, V., Lacombe, M.L., Véron, M., Janin, J. J. Mol. Biol. (1991) [Pubmed]
 
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