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SPRED proteins provide a NF-ty link to Ras suppression
Andrea I McClatchey1, Karen Cichowski
1Massachusetts General Hospital Center for Cancer Research, Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129, USA. mcclatch@helix.mgh.harvard.edu
Genes & Development
|July 18, 2012
Summary
Spred1 recruits neurofibromin to the cell membrane, effectively reducing Ras signaling. This finding explains the shared symptoms between SPRED1 and neurofibromatosis 1 disorders.
Area of Science:
- Molecular Biology
- Cell Signaling
- Genetics
Background:
- Mutations in SPRED1 and NF1 genes cause related human disorders.
- Neurofibromin (NF1) is a Ras GTPase-activating protein that limits Ras activity.
- Spred proteins also negatively regulate Ras signaling, but their mechanism is unclear.
Purpose of the Study:
- To elucidate the mechanism by which Spred1 regulates Ras signaling.
- To explain the overlapping clinical features of SPRED1 and NF1 disorders.
Main Methods:
- Investigated the interaction between Spred1 and neurofibromin.
- Examined the effect of Spred1 on Ras activity at the cellular membrane.
Main Results:
- Spred1 recruits neurofibromin to the cell membrane.
- This recruitment dampens growth factor-induced Ras activity.
Conclusions:
- Spred1 acts as an adaptor protein, bringing neurofibromin to the membrane to inhibit Ras.
- This mechanism provides a molecular basis for the clinically related SPRED1 and NF1 disorders.
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