Role of NF1 and NF2 in Signaling and Transformation
Annual rept. 15 Sep 1998-14 Sep 1999
NORTH CAROLINA UNIV AT CHAPEL HILL
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During the past year of our grant we have concentrated on specific aim three. During the first year, we determined that NF2 blocks Ras transformation, in part, by blocking the action of the Rac small GTPase. Therefore, we focused our efforts on futher assessing the mechanism by which NF2 antagonizes Rac signaling and function. Progress has been made in two main directions. First, we extended our previous analyses and determined that NF2 can block multiple Rac-mediated signaling activities. This suggests that NF2 inhibition of Rac function is not due to inhibition of a subset of Rac signaling events and argues that NF2 may directly modulate Rac itself. This outcome was an unexpected. Second, based on an observation by our collaborators, Rac was found to cause phosphorylation of NF2. The consequences of this phosphorylation on NF2 negative modulation of Rac transforming activity was determined. When taken together, these observations may provide a key clue regarding the tumor suppressing function of NF2. Rac function has been found to be necessary for the transforming actions of Ras and other oncoproteins e.g., Mas, Vav, Abl, Fps. Therefore, if NF2 is a negative modulator of Rac function, it may serve as a negative modulator of growth regulation by a spectrum of growth promoting signaling proteins.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research