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A role for Abl in Notch signaling
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Neuron
|May 15, 1998
Summary
Notch and Abl mutations cause synthetic lethality and axon defects in Drosophila. The Abl accessory protein Disabled may regulate Notch signaling in axons.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Abl is an axonal tyrosine kinase.
- Notch is a receptor with an incompletely understood signaling pathway.
Purpose of the Study:
- Investigate the interaction between Notch and Abl mutations.
- Determine the role of Notch and Abl in axon extension.
Main Methods:
- Studied synergistic genetic interactions between Notch and abl mutations in Drosophila.
- Examined axonal defects and cell identity.
- Investigated the localization of Notch in growth cones.
- Performed in vitro binding assays between Disabled and Notch.
Main Results:
- Notch and abl mutations exhibit synthetic lethality and axon extension defects.
- Axonal aberrations were not explained by changes in cell identity.
- Notch is present in the growth cones of extending axons.
- The Abl accessory protein Disabled binds to a Notch signaling domain in vitro.
Conclusions:
- Notch and Abl signaling pathways are functionally linked in Drosophila axons.
- Disabled and Abl may regulate Notch signaling in axons by binding to the Notch intracellular domain.