Accession Number : ADA324302

Title :   A Genetic Analysis of NFl Function in Drosophila Melanogaster (Neurofibromatosis).

Descriptive Note : Final rept. 22 Sep 93-21 Sep 96,

Corporate Author : MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s) : Hariharan, Iswar K.

PDF Url : ADA324302

Report Date : OCT 1996

Pagination or Media Count : 21

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.

Descriptors :   *MUTATIONS, *CELLS(BIOLOGY), *GENETICS, *NUCLEOTIDES, *DROSOPHILA, *FIBROSIS, PROTEINS, RESPONSE, SIGNALS, VIABILITY, ANIMALS, HUMAN BODY, IN VIVO ANALYSIS, ESCAPE SYSTEMS, WILDLIFE, SENSE ORGANS, TYROSINE, PHOSPHORUS TRANSFERASES.

Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE