Novel Molecular Interactions and Biological Functions of the Neurofibromatosis 2 Tumor Suppressor Protein, Merlin
Abstract
The project studies molecular functions of neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin. Phosphorylation is an important mechanism in theregulation of both proteins. We have studied the interplay between protein kinase A (PKA) andmerlin. We identified an N-terminal phosphorylation site at merlin S10. Phosphorylation of S10 does not affect phosphorylation of S518 or ezrin binding. It affects, however, actin dynamics and cell morphology and migration in Nf2 -/- mouse embryonic fibroblasts (MEF) and Schwann cells. This suggests a role for merlinin mediating PKA induced changes of the actin cytoskeleton. We also show a link between PKA and calpain in the regulation of merlin cleavage and subcellular localization. We previously showed that oncogenic tyronsine kinase Src phosphorylates ezrin at Y477. Using reconstituted MEF cells from ezrin -/- mice we studied the biological importance of Y477 phosphorylation. Our results show that ezrin is a key regulator of Src induced malignant behavior in three dimentional culture conditions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2008
- Accession Number
- ADA483204
Entities
People
- Olli Carpen
Organizations
- University of Helsinki