Novel Molecular Interactions and Biological Functions of the Neurofibromatosis 2 Tumor Suppressor Protein, Merlin
Final rept. 29 Jul 2005-28 Jul 2008
HELSINKI UNIV (FINLAND)
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The project has studied the functions of the neurofibromatosis 2 tumor suppressor protein merlin and the related ERM protein ezrin. We identified novel binding partners and functions for both proteins. Merlin was shown to regulate both the microtubule and actin cytoskeleton. Two important kinases, protein kinase A PKA and AKT, were shown to phosphorylate merlin at S10. This phosphorylation affects actin dynamics, cell morphology and migration of mouse embryonic fibroblasts MEF and Schwann cells. Thus, merlin may serve as a regulator of PKA and AKT induced changes in actin cytoskeleton. We identified a link between merlin and cell cycle control by demonstrating a novel functional interaction between merlin and HEI10. In studies of the biological activities of ezrin we discovered that oncogenic tyrosine kinases Src and c-Met phosphorylate 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 dimensional culture conditions.
- Anatomy and Physiology
- Medicine and Medical Research