Interaction between two isoforms of the NF2 tumor suppressor protein, merlin, and between merlin and ezrin, suggests modulation of ERM proteins by merlin.

作者: Jin-Jun Meng , D.J. Lowrie , Hao Sun , Emily Dorsey , Patricia D. Pelton

DOI: 10.1002/1097-4547(20001115)62:4<491::AID-JNR3>3.0.CO;2-D

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摘要: The product of the neurofibromatosis type II (NF2) tumor suppressor gene, merlin, is closely related to ezrin-radixin-moesin (ERM) family, a group proteins believed link cytoskeleton plasma membrane. Mutation in NF2 locus associated with Schwann cell tumors (schwannomas). two predominant merlin isoforms, I and II, differ only carboxy-terminal 16 residues isoform anti-proliferative. Merlin lacks an actin-binding domain conserved among ezrin, radixin moesin. Because ezrin moesin are co-expressed cells, all homodimerize, we have examined whether dimerize one another. We found by immunoprecipitation yeast two-hybrid assays that both isoforms interact ezrin. interaction occurs head-to-tail orientation, amino-terminal half protein interacting other. behave differently their Isoform binds whose carboxy-terminus exposed, whereas regardless open or closed conformation. heterodimerization much stronger than between either can inhibit merlin-ezrin binding. This suggests that, vivo, dimerization could regulate merlin-ERM interaction, thus indirectly other interactions involving ERM proteins. J. Neurosci. Res. 62:491–502, 2000. © 2000 Wiley-Liss, Inc.

参考文章(55)
K.L. Gould, A. Bretscher, F.S. Esch, T. Hunter, cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. The EMBO Journal. ,vol. 8, pp. 4133- 4142 ,(1989) , 10.1002/J.1460-2075.1989.TB08598.X
J. Gusella, D. Pinney, C. Gonzalez-Agosti, W. Hobbs, V. Ramesh, R. Beauchamp, L. Xu, The merlin tumor suppressor localizes preferentially in membrane ruffles. Oncogene. ,vol. 13, pp. 1239- 1247 ,(1996)
Mohini Lutchman, Guy A. Rouleau, The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Cancer Research. ,vol. 55, pp. 2270- 2274 ,(1995)
H. Maruta, Anjali Tikoo, M. Varga, Vijaya Ramesh, J. Gusella, An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). Journal of Biological Chemistry. ,vol. 269, pp. 23387- 23390 ,(1994) , 10.1016/S0021-9258(17)31525-9
M.F. White, C.R. Kahn, The insulin signaling system. Journal of Biological Chemistry. ,vol. 269, pp. 1- 4 ,(1994) , 10.1016/S0021-9258(17)42297-6
G I Evan, G K Lewis, G Ramsay, J M Bishop, Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Molecular and Cellular Biology. ,vol. 5, pp. 3610- 3616 ,(1985) , 10.1128/MCB.5.12.3610
Hiroyuki Kamiguchi, Vance Lemmon, NEURAL CELL ADHESION MOLECULE L1 : SIGNALING PATHWAYS AND GROWTH CONE MOTILITY Journal of Neuroscience Research. ,vol. 49, pp. 1- 8 ,(1997) , 10.1002/(SICI)1097-4547(19970701)49:1<1::AID-JNR1>3.0.CO;2-H
Daniel R. Scoles, Duong P. Huynh, Paul A. Morcos, Eric R. Coulsell, Nicole G.G. Robinson, Fuyuhiko Tamanoi, Stefan M. Pulst, Neurofibromatosis 2 tumour suppressor schwannomin interacts with βII-spectrin Nature Genetics. ,vol. 18, pp. 354- 359 ,(1998) , 10.1038/NG0498-354
A G Knudson, Antioncogenes and human cancer Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 10914- 10921 ,(1993) , 10.1073/PNAS.90.23.10914
Jin-Jun Meng, Elayne A. Bornslaeger, Kathleen J. Green, Peter M. Steinert, Wallace Ip, Two-hybrid Analysis Reveals Fundamental Differences in Direct Interactions between Desmoplakin and Cell Type-specific Intermediate Filaments * Journal of Biological Chemistry. ,vol. 272, pp. 21495- 21503 ,(1997) , 10.1074/JBC.272.34.21495