Dosage-sensitive modifiers of Drosophila abl tyrosine kinase function: prospero, a regulator of axonal outgrowth, and disabled, a novel tyrosine kinase substrate.
In the absence of the Drosophila abl protein-tyrosine kinase (PTK), loss-of-function mutations in either disabled or prospero have dominant phenotypic effects on embryonic development. Molecular and genetic characterizations indicate that the products of these genes interact with the abl PTK by different mechanisms. The interaction between abl and prospero, which encodes a nuclear protein required for correct axonal outgrowth, is likely to be indirect. In contrast, the product of disabled may be a substrate for the abl PTK. The disabled protein is colocalized with abl in axons, its predicted amino acid sequence contains 10 motifs similar to the major autophosphorylation site of abl, and the protein is recognized by antibodies to phosphotyrosine.
Gertler
F B
FB
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Hill
K K
KK
Clark
M J
MJ
Hoffmann
F M
FM
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D005260:Female; D015723:Gene Library; D005809:Genes, Regulator; D016313:Genes, abl; D005838:Genotype; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009420:Nervous System / Q000254:growth & development; D009687:Nuclear Proteins / Q000378:metabolism; D016374:Oncogene Proteins v-abl / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D013379:Substrate Specificity; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016374:Oncogene Proteins v-abl; C080216:dab protein, Drosophila; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases