title: The merlin tumor suppressor interacts with Ral guanine nucleotide dissociation stimulator and inhibits its activity.
abstract: Neurofibromatosis type 2 (NF2) is the most commonly mutated gene in benign tumors of the human nervous system such as schwannomas and meningiomas. The NF2 gene encodes a protein called schwannomin or merlin, which is involved in regulating cell growth and proliferation through protein-protein interactions with various cellular proteins. In order to better understand the mechanism by which merlin exerts its function, yeast two-hybrid screening was performed and Ral guanine nucleotide dissociation stimulator (RalGDS), a downstream molecule of Ras, was identified as a merlin-binding protein. The direct interaction between merlin and RalGDS was confirmed both in vitro and in the NIH3T3 cells. The domain analyses revealed that the broad C-terminal region of merlin (aa 141-595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RalGDS. Functional studies showed that merlin inhibits the RalGDS-induced RalA activation, the colony formation and the cell migration in mammalian cells. These results suggest that merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals.
authors: Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, Korea.
authors: Chung Hun
authors: CH
authors: Ryu
authors: Sae-Woong
authors: SW
authors: Kim
authors: Kyu Hwa
authors: KH
authors: Lee
authors: Joo Yong
authors: JY
authors: Lee
authors: Hongtae
authors: H
authors: Kim
authors: Woon Kyu
authors: WK
authors: Lee
authors: Byung Hyune
authors: BH
authors: Choi
authors: Young
authors: Y
authors: Lim
authors: Young Hoon
authors: YH
authors: Kim
authors: Kweon-Haeng
authors: KH
authors: Lee
authors: Tae-Kon
authors: TK
authors: Hwang
authors: Tae-Youn
authors: TY
authors: Jun
authors: Hyoung Kyun
authors: HK
authors: Rha
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D003114:Colony-Forming Units Assay; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D041681:NIH 3T3 Cells; D025581:Neurofibromin 2 / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D020726:ral Guanine Nucleotide Exchange Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D025581:Neurofibromin 2; D020726:ral Guanine Nucleotide Exchange Factor