The receptor protein tyrosine phosphatase PTP69D antagonizes Abl tyrosine kinase to guide axons in Drosophila.
During Drosophila embryogenesis, both the cytoplasmic Abelson tyrosine kinase (Abl) and the membrane bound tyrosine phosphatase PTP69D are required for proper guidance of CNS and motor axons. We provide evidence that PTP69D modulates signaling by Abl and its antagonist, Ena. An Abl loss-of function mutation dominantly suppresses most Ptp69D mutant phenotypes including larval/pupal lethality and CNS and motor axon defects, while increased Abl and decreased Ena expression dramatically increase the expressivity of Ptp69D axonal defects. In contrast, Ptp69D mutations do not affect Abl mutant phenotypes. These results support the hypothesis that PTP69D antagonizes the Abl/Ena genetic pathway, perhaps as an upstream regulator. We also find that mutation of the gene encoding the cytoplasmic Src64B tyrosine kinase exacerbates Ptp69D phenotypes, suggesting that two different cytoplasmic tyrosine kinases, Abl and Src64B, modify PTP69D-mediated axon patterning in quite different ways.
Song
Jeong K
JK
Axon Guidance and Neural Connectivity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg 37 Room 1016, 37 Convent Drive, Bethesda, MD 20892, USA.
Giniger
Edward
E
Desai
Chand J
CJ
D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology*; D019521:Body Patterning; D002490:Central Nervous System / Q000196:embryology* / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000201:enzymology; D029721:Drosophila Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005804:Genes, Lethal; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092744:ENA-VASP proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila; C075699:Src64B protein, Drosophila; C482451:PTP69D protein, Drosophila; D054557:Receptor-Like Protein Tyrosine Phosphatases