A Genetic Analysis of NFl Function in Drosophila Melanogaster (Neurofibromatosis).
Abstract
The human neurofibromatosis type 1 (NF1) protein contains a RasGAP domain and is believed to restrain cell proliferation by negatively regulating Ras-mediated signalling. We have characterized a Drosophila NF1 homologue encoding a protein that is 60% identical to the human NF1 protein over its entire length and generated loss-of-function mutations. Flies lacking NF1 are viable and Ras1-mediated signalling downstream of the sevenless and torso receptor tyrosine kinases is normal, indicating that Drosophila NF1 is not a crucial Ras1 regulator. However, combined loss of NF1 and another Drosophila RasGAP, Gap1, is lethal, arguing that NF1 may be a redundant Ras1 regulator in vivo. Mutants lacking NF1 are 25-30% smaller than wild type animals during all post-embryonic developmental stages and mutants also display a diminished escape response. Remarkably, the size defect is not modified by manipulating Ras1 pathway signalling but is rescued by providing increased levels of PKA activity. Thus NF1 may modulate both PKA and Ras signalling in vivo and could conceivably provide a link between these signalling pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADA324302
Entities
People
- Iswar K. Hariharan
Organizations
- Massachusetts General Hospital