The expanding family of FERM proteins

Biochemical Journal

Volumn 452, Issue 2, 2013, Pages 183-193

  Moleirinho, Susana ^a,b   Tilston Lunel, Andrew ^b   Angus, Liselotte ^b   Gunn Moore, Frank ^b   Reynolds, Paul A ^a  

^a UNIVERSITY OF ST ANDREWS   (United Kingdom)

^b UNIVERSITY OF ST ANDREWS   (United Kingdom)

Author keywords

4.1 ezrin radixin moesin (FERM) domain; Ezrin; Ezrin radixin moesin (ERM); FRMD genes; Par3; Willin

Indexed keywords

DROSOPHILA PROTEIN; EZRIN; FRMD3 PROTEIN; FRMD4A PROTEIN; FRMD5 PROTEIN; FRMD6 PROTEIN; FRMD7 PROTEIN; FRMPD1 PROTEIN; FRMPD2 PROTEIN; MOESIN; PLECKSTRIN; PROTEIN; RADIXIN; UNCLASSIFIED DRUG;

ALLERGIC AIRWAY INFLAMMATION; CELL CONTACT; CELL MEMBRANE; CELLULAR DISTRIBUTION; CONFORMATIONAL TRANSITION; CONGENITAL NYSTAGMUS; CONTACT INHIBITION; CRYSTAL STRUCTURE; DISEASE ASSOCIATION; DNA SEQUENCE; EPITHELIAL MESENCHYMAL TRANSITION; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; HEART FAILURE; HELA CELL; HUMAN; HUMAN GENOME; MEMBRANE BINDING; MOLECULAR WEIGHT; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; STRUCTURAL HOMOLOGY; TIGHT JUNCTION; TRANSIENT TRANSFECTION;

CYTOSKELETAL PROTEINS; FORECASTING; HUMANS; MEMBRANE PROTEINS; MULTIGENE FAMILY; PROTEIN STRUCTURE, TERTIARY;

EID: 84877770420     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20121642     Document Type: Review

References (138)

1. Amieva, M. R., Wilgenbus, K. K. and Furthmayr, H. (1994) Radixin is a component of hepatocyte microvilli in situ. Exp. Cell Res. 210, 140-144
2. Sun, C. X., Robb, V. A. and Gutmann, D. H. (2002) Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J. Cell Sci. 115, 3991-4000
3. Diakowski, W., Grzybek, M. and Sikorski, A. F. (2006) Protein 4.1, a component of the erythrocyte membrane skeleton and its related homologue proteins forming the protein 4.1/FERM superfamily. Folia Histochem. Cytobiol. 44, 231-248
4. Frame, M. C., Patel, H., Serrels, B., Lietha, D. and Eck, M. J. (2010) The FERM domain: organizing the structure and function of FAK. Nat. Rev. Mol. Cell Biol. 11, 802-814
5. Arpin, M., Chirivino, D., Naba, A. and Zwaenepoel, I. (2011) Emerging role for ERM proteins in cell adhesion and migration. Cell Adhes. Migr. 5, 199-206
6. Fehon, R. G., McClatchey, A. I. and Bretscher, A. (2010) Organizing the cell cortex: the role of ERM proteins. Nat. Rev. Mol. Cell Biol. 11, 276-287
7. Stamenkovic, I. and Yu, Q. (2010) Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival. Curr. Protein Pept. Sci. 11, 471-484
8. McClatchey, A. I. and Fehon, R. G. (2009) Merlin and the ERM proteins: regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol. 19, 198-206
9. McClatchey, A. I. (2003) Merlin and ERM proteins: unappreciated roles in cancer development? Nat. Rev. Cancer 3, 877-883
10. Bretscher, A., Edwards, K. and Fehon, R. G. (2002) ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3, 586-599
11. Saotome, I., Curto, M. and McClatchey, A. I. (2004) Ezrin is essential for epithelial organization and villus morphogenesis in the developing intestine. Dev. Cell 6, 855-864
12. Berryman, M., Franck, Z. and Bretscher, A. (1993) Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J. Cell Sci. 105, 1025-1043
13. Schwartz-Albiez, R., Merling, A., Spring, H., Moller, P. and Koretz, K. (1995) Differential expression of the microspike-associated protein moesin in human tissues. Eur. J. Cell Biol. 67, 189-198
14. Wang, W., Soroka, C. J., Mennone, A., Rahner, C., Harry, K., Pypaert, M. and Boyer, J. L. (2006) Radixin is required to maintain apical canalicular membrane structure and function in rat hepatocytes. Gastroenterology 131, 878-884
15. Rouleau, G. A., Merel, P., Lutchman, M., Sanson, M., Zucman, J., Marineau, C., Hoang-Xuan, K., Demczuk, S., Desmaze, C., Plougastel, B. et al. (1993) Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363, 515-521
16. Trofatter, J. A., MacCollin, M. M., Rutter, J. L., Murrell, J. R., Duyao, M. P., Parry, D. M., Eldridge, R., Kley, N., Menon, A. G., Pulaski, K. et al. (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72, 791-800
17. McClatchey, A. I., Saotome, I., Mercer, K., Crowley, D., Gusella, J. F., Bronson, R. T. and Jacks, T. (1998) Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12, 1121-1133
18. Giovannini, M., Robanus-Maandag, E., van der Valk, M., Niwa-Kawakita, M., Abramowski, V., Goutebroze, L., Woodruff, J. M., Berns, A. and Thomas, G. (2000) Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev. 14, 1617-1630
19. Mak, H., Naba, A., Varma, S., Schick, C., Day, A., SenGupta, S. K., Arpin, M. and Elliott, B. E. (2012) Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells. BMC Cancer 12, 82
20. Li, J., Tu, Y., Wen, J., Yao, F., Wei, W. and Sun, S. (2010) Role for ezrin in breast cancer cell chemotaxis to CCL5. Oncol. Rep. 24, 965-971
21. Elliott, B. E., Meens, J. A., SenGupta, S. K., Louvard, D. and Arpin, M. (2005) The membrane cytoskeletal crosslinker ezrin is required for metastasis of breast carcinoma cells. Breast Cancer Res. 7, R365-R373
22. Li, Q., Wu, M., Wang, H., Xu, G., Zhu, T., Zhang, Y., Liu, P., Song, A., Gang, C., Han, Z. et al. (2008) Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells. Cancer Lett. 261, 55-63
23. Sarrio, D., Rodriguez-Pinilla, S. M., Dotor, A., Calero, F., Hardisson, D. and Palacios, J. (2006) Abnormal ezrin localization is associated with clinicopathological features in invasive breast carcinomas. Breast Cancer Res. Treat. 98, 71-79
24. Madan, R., Brandwein-Gensler, M., Schlecht, N. F., Elias, K., Gorbovitsky, E., Belbin, T. J., Mahmood, R., Breining, D., Qian, H., Childs, G. et al. (2006) Differential tissue and subcellular expression of ERM proteins in normal and malignant tissues: cytoplasmic ezrin expression has prognostic signficance for head and neck squamous cell carcinoma. Head Neck 28, 1018-1027
25. Schlecht, N. F., Brandwein-Gensler, M., Smith, R. V., Kawachi, N., Broughel, D., Lin, J., Keller, C. E., Reynolds, P. A., Gunn-Moore, F. J., Harris, T. et al. (2012) Cytoplasmic ezrin and moesin correlate with poor survival in head and neck squamous cell carcinoma. Head Neck Pathol. 6, 232-243
26. Smith, W. J., Nassar, N., Bretscher, A., Cerione, R. A. and Karplus, P. A. (2003) Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions. J. Biol. Chem. 278, 4949-4956
27. Edwards, S. D. and Keep, N. H. (2001) The 2.7 Å crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation. Biochemistry 40, 7061-7068
28. Pearson, M. A., Reczek, D., Bretscher, A. and Karplus, P. A. (2000) Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101, 259-270
29. Mori, T., Kitano, K., Terawaki, S., Maesaki, R. and Hakoshima, T. (2007) Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of adhesion molecule CD44. Acta Crystallogr., Sect. F: Struct. Biol. Crystal. Commun. 63, 844-847
30. Takai, Y., Kitano, K., Terawaki, S., Maesaki, R. and Hakoshima, T. (2007) Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tails of adhesion molecules CD43 and PSGL-1. Acta Crystallogr., Sect. F: Struct. Biol. Crystal. Commun. 63, 49-51
31. Hamada, K., Shimizu, T., Matsui, T., Tsukita, S. and Hakoshima, T. (2000) Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. EMBO J. 19, 4449-4462
32. Martel, V., Racaud-Sultan, C., Dupe, S., Marie, C., Paulhe, F., Galmiche, A., Block, M. R. and Albiges-Rizo, C. (2001) Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. J. Biol. Chem. 276, 21217-21227
33. Kusunoki, H. and Kohno, T. (2009) Solution structure and glycophorin C binding studies of the protein 4.1R FERM α-lobe domain. Proteins 76, 255-260
34. Hirao, M., Sato, N., Kondo, T., Yonemura, S., Monden, M., Sasaki, T., Takai, Y. and Tsukita, S. (1996) Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J. Cell Biol. 135, 37-51
35. Morrison, H., Sherman, L. S., Legg, J., Banine, F., Isacke, C., Haipek, C. A., Gutmann, D. H., Ponta, H. and Herrlich, P. (2001) The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15, 968-980
36. Morrison, H., Sperka, T., Manent, J., Giovannini, M., Ponta, H. and Herrlich, P. (2007) Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res. 67, 520-527
37. Tsukita, S., Oishi, K., Sato, N., Sagara, J. and Kawai, A. (1994) ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J. Cell Biol. 126, 391-401
38. Ramesh, V. (2004) Merlin and the ERM proteins in Schwann cells, neurons and growth cones. Nat. Rev. Neurosci. 5, 462-470
39. Lee, H. S., Bellin, R. M., Walker, D. L., Patel, B., Powers, P., Liu, H., Garcia-Alvarez, B., de Pereda, J. M., Liddington, R. C., Volkmann, N. et al. (2004) Characterization of an actin-binding site within the talin FERM domain. J. Mol. Biol. 343, 771-784
40. Gunn-Moore, F. J., Hill, M., Davey, F., Herron, L. R., Tait, S., Sherman, D. and Brophy, P. J. (2006) A functional FERM domain binding motif in neurofascin. Mol. Cell. Neurosci. 33, 441-446
41. Chishti, A. H., Kim, A. C., Marfatia, S. M., Lutchman, M., Hanspal, M., Jindal, H., Liu, S. C., Low, P. S., Rouleau, G. A., Mohandas, N. et al. (1998) The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem. Sci. 23, 281-282
42. Cai, X., Lietha, D., Ceccarelli, D. F., Karginov, A. V., Rajfur, Z., Jacobson, K., Hahn, K. M., Eck, M. J. and Schaller, M. D. (2008) Spatial and temporal regulation of focal adhesion kinase activity in living cells. Mol. Cell. Biol. 28, 201-214
43. Lemmon, M. A. (2008) Membrane recognition by phospholipid-binding domains. Nat. Rev. Mol. Cell Biol. 9, 99-111
44. Leonard, T. A. and Hurley, J. H. (2011) Regulation of protein kinases by lipids. Curr. Opin. Struct. Biol. 21, 785-791
45. Lietha, D., Cai, X., Ceccarelli, D. F., Li, Y., Schaller, M. D. and Eck, M. J. (2007) Structural basis for the autoinhibition of focal adhesion kinase. Cell 129, 1177-1187
46. An, N., Blumer, J. B., Bernard, M. L. and Lanier, S. M. (2008) The PDZ and band 4.1 containing protein Frmpd1 regulates the subcellular location of activator of G-protein signaling 3 and its interaction with G-proteins. J. Biol. Chem. 283, 24718-24728
47. Nagayama, S., Iiizumi, M., Katagiri, T., Toguchida, J. and Nakamura, Y. (2004) Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas. Oncogene 23, 5551-5557
48. Stenzel, N., Fetzer, C. P., Heumann, R. and Erdmann, K. S. (2009) PDZ-domain-directed basolateral targeting of the peripheral membrane protein FRMPD2 in epithelial cells. J. Cell Sci. 122, 3374-3384
49. Genevet, A. and Tapon, N. (2011) The Hippo pathway and apico-basal cell polarity. Biochem. J. 436, 213-224
50. Gassama-Diagne, A., Yu, W., ter Beest, M., Martin-Belmonte, F., Kierbel, A., Engel, J. and Mostov, K. (2006) Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells. Nat. Cell Biol. 8, 963-970
51. Martin-Belmonte, F., Gassama, A., Datta, A., Yu, W., Rescher, U., Gerke, V. and Mostov, K. (2007) PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128, 383-397
52. Astle, M. V., Seaton, G., Davies, E. M., Fedele, C. G., Rahman, P., Arsala, L. and Mitchell, C. A. (2006) Regulation of phosphoinositide signaling by the inositol polyphosphate 5-phosphatases. IUBMB Life 58, 451-456
53. Mitchell, C. A., Gurung, R., Kong, A. M., Dyson, J. M., Tan, A. and Ooms, L. M. (2002) Inositol polyphosphate 5-phosphatases: lipid phosphatases with flair. IUBMB Life 53, 25-36
54. Ni, X., Ji, C., Cao, G., Cheng, H., Guo, L., Gu, S., Ying, K., Zhao, R. C. and Mao, Y. (2003) Molecular cloning and characterization of the protein 4.1O gene, a novel member of the protein 4.1 family with focal expression in ovary. J. Hum. Genet. 48, 101-106
55. Haase, D., Meister, M., Muley, T., Hess, J., Teurich, S., Schnabel, P., Hartenstein, B. and Angel, P. (2007) FRMD3, a novel putative tumour suppressor in NSCLC. Oncogene 26, 4464-4468
56. Freedman, B. I., Langefeld, C. D., Lu, L., Divers, J., Comeau, M. E., Kopp, J. B., Winkler, C. A., Nelson, G. W., Johnson, R. C., Palmer, N. D. et al. (2011) Differential effects of MYH9 and APOL1 risk variants on FRMD3 association with Diabetic ESRD in African Americans. PLoS Genet. 7, e1002150
57. Hu, C., Zhang, R., Yu, W., Wang, J., Wang, C., Pang, C., Ma, X., Bao, Y., Xiang, K. and Jia, W. (2011) CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. Diabetes 60, 3085-3089
58. Maeda, S., Araki, S., Babazono, T., Toyoda, M., Umezono, T., Kawai, K., Imanishi, M., Uzu, T., Watada, H., Suzuki, D. et al. (2010) Replication study for the association between four loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. Diabetes 59, 2075-2079
59. Pezzolesi, M. G., Poznik, G. D., Mychaleckyj, J. C., Paterson, A. D., Barati, M. T., Klein, J. B., Ng, D. P., Placha, G., Canani, L. H., Bochenski, J. et al. (2009) Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes. Diabetes 58, 1403-1410
60. Ikenouchi, J. and Umeda, M. (2010) FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex. Proc. Natl. Acad. Sci. U.S.A. 107, 748-753
61. Suzuki, A. and Ohno, S. (2006) The PAR-aPKC system: lessons in polarity. J. Cell Sci. 119, 979-987
62. Lambert, J. C., Grenier-Boley, B., Harold, D., Zelenika, D., Chouraki, V., Kamatani, Y., Sleegers, K., Ikram, M. A., Hiltunen, M., Reitz, C. et al. (2012) Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Mol. Psychiatry, doi:10.1038/mp.2012.14
63. Goldie, S. J., Mulder, K. W., Tan, D. W., Lyons, S. K., Sims, A. H. and Watt, F. M. (2012) FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis. Cancer Res. 72, 3424-3436
64. Klarlund, J. K., Holik, J., Chawla, A., Park, J. G., Buxton, J. and Czech, M. P. (2001) Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF exchange factor GRP1. J. Biol. Chem. 276, 40065-40070
65. Watford, W. T., Li, D., Agnello, D., Durant, L., Yamaoka, K., Yao, Z. J., Ahn, H. J., Cheng, T. P., Hofmann, S. R., Cogliati, T. et al. (2006) Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiation. Mol. Cell. Biol. 26, 6623-6632
66. DiNitto, J. P., Lee, M. T., Malaby, A. W. and Lambright, D. G. (2010) Specificity and membrane partitioning of Grsp1 signaling complexes with Grp1 family Arf exchange factors. Biochemistry 49, 6083-6092
67. Cappola, T. P., Li, M., He, J., Ky, B., Gilmore, J., Qu, L., Keating, B., Reilly, M., Kim, C. E., Glessner, J. et al. (2010) Common variants in HSPB7 and FRMD4B associated with advanced heart failure. Circ.: Cardiovasc. Genet. 3, 147-154
68. Matkovich, S. J., Van Booven, D. J., Cappola, T. P. and Dorn, 2nd, G. W. (2010) Association of an intronic, but not any exonic, FRMD4B sequence variant and heart failure. Clin. Transl. Sci. 3, 134-139
69. Brazdova, M., Quante, T., Togel, L., Walter, K., Loscher, C., Tichy, V., Cincarova, L., Deppert, W. and Tolstonog, G. V. (2009) Modulation of gene expression in U251 glioblastoma cells by binding of mutant p53 R273H to intronic and intergenic sequences. Nucleic Acids Res. 37, 1486-1500
70. Seo, D. C., Sung, J. M., Cho, H. J., Yi, H., Seo, K. H., Choi, I. S., Kim, D. K., Kim, J. S., El-Aty, A. A. and Shin, H. C. (2007) Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells. Mol. Cancer 6, 75
71. Wang, T., Pei, X., Zhan, J., Hu, J., Yu, Y. and Zhang, H. (2012) FERM-containing protein FRMD5 is a p120-catenin interacting protein that regulates tumor progression. FEBS Lett. 586, 3044-3050
72. Gunn-Moore, F. J., Welsh, G. I., Herron, L. R., Brannigan, F., Venkateswarlu, K., Gillespie, S., Brandwein-Gensler, M., Madan, R., Tavare, J. M., Brophy, P. J. et al. (2005) A novel 4.1 ezrin radixin moesin (FERM)-containing protein, 'Willin'. FEBS Lett. 579, 5089-5094
73. Tait, S., Gunn-Moore, F., Collinson, J. M., Huang, J., Lubetzki, C., Pedraza, L., Sherman, D. L., Colman, D. R. and Brophy, P. J. (2000) An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J. Cell Biol. 150, 657-666
74. Charles, P., Tait, S., Faivre-Sarrailh, C., Barbin, G., Gunn-Moore, F., Denisenko-Nehrbass, N., Guennoc, A. M., Girault, J. A., Brophy, P. J. and Lubetzki, C. (2002) Neurofascin is a glial receptor for the paranodin/Caspr- contactin axonal complex at the axoglial junction. Curr. Biol. 12, 217-220
75. Davey, F., Hill, M., Falk, J., Sans, N. and Gunn-Moore, F. J. (2005) Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone-glial related cell adhesion molecule. J. Neurochem. 94, 1243-1253
76. Hamaratoglu, F., Willecke, M., Kango-Singh, M., Nolo, R., Hyun, E., Tao, C., Jafar-Nejad, H. and Halder, G. (2006) The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8, 27-36
77. Batchelor, C. L., Woodward, A. M. and Crouch, D. H. (2004) Nuclear ERM (ezrin, radixin, moesin) proteins: regulation by cell density and nuclear import. Exp. Cell Res. 296, 208-222
78. Di Cristofano, C., Leopizzi, M., Miraglia, A., Sardella, B., Moretti, V., Ferrara, A., Petrozza, V. and Della Rocca, C. (2010) Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell. Mod. Pathol. 23, 1012-1020
79. Angus, L., Moleirinho, S., Herron, L., Sinha, A., Zhang, X., Niestrata, M., Dholakia, K., Prystowsky, M. B., Harvey, K. F., Reynolds, P. A. and Gunn-Moore, F. J. (2012) Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP. Oncogene 31, 238-250
80. Matsui, T., Maeda, M., Doi, Y., Yonemura, S., Amano, M., Kaibuchi, K. and Tsukita, S. (1998) Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J. Cell Biol. 140, 647-657
81. Oshiro, N., Fukata, Y. and Kaibuchi, K. (1998) Phosphorylation of moesin by rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J. Biol. Chem. 273, 34663-34666
82. Ng, T., Parsons, M., Hughes, W. E., Monypenny, J., Zicha, D., Gautreau, A., Arpin, M., Gschmeissner, S., Verveer, P. J., Bastiaens, P. I. and Parker, P. J. (2001) Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility. EMBO J. 20, 2723-2741
83. Wald, F., Oriolo, A., Mashukova, A., Hamid, A. and Salas, P. (2008) Ezrin phosphorylation in T567 is mediated by atypical PKC in intestinal epithelial cells. Inflammatory Bowel Diseases 14, S38-S38
84. Pietromonaco, S. F., Simons, P. C., Altman, A. and Elias, L. (1998) Protein kinase C-θ phosphorylation of moesin in the actin-binding sequence. J. Biol. Chem. 273, 7594-7603
85. Nakamura, N., Oshiro, N., Fukata, Y., Amano, M., Fukata, M., Kuroda, S., Matsuura, Y., Leung, T., Lim, L. and Kaibuchi, K. (2000) Phosphorylation of ERM proteins at filopodia induced by Cdc42. Genes Cells 5, 571-581
86. Carreno, S., Kouranti, I., Glusman, E. S., Fuller, M. T., Echard, A. and Payre, F. (2008) Moesin and its activating kinase Slik are required for cortical stability and microtubule organization in mitotic cells. J. Cell Biol. 180, 739-746
87. Kunda, P., Pelling, A. E., Liu, T. and Baum, B. (2008) Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis. Curr. Biol. 18, 91-101
88. Belkina, N. V., Liu, Y., Hao, J. J., Karasuyama, H. and Shaw, S. (2009) LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 106, 4707-4712
89. Liu, D., Ge, L., Wang, F., Takahashi, H., Wang, D., Guo, Z., Yoshimura, S. H., Ward, T., Ding, X., Takeyasu, K. and Yao, X. (2007) Single-molecule detection of phosphorylation-induced plasticity changes during ezrin activation. FEBS Lett. 581, 3563-3571
90. Ma, L., Liu, Y. P., Zhang, X. H., Xing, L. X., Wang, J. L. and Geng, C. Z. (2009) Effect of RhoA signaling transduction on expression of Ezrin in breast cancer cell lines. Aizheng 28, 108-111 90a
91. Angus, L. (2011) Willin as a Novel 4.1 Ezrin Radixin Moesin (FERM) Domain Protein in the Mammalian Hippo Signalling Pathway. Ph.D. Thesis, University of St Andrews, St Andrews, Fife, U.K.
92. Boedigheimer, M. and Laughon, A. (1993) Expanded: a gene involved in the control of cell proliferation in imaginal discs. Development 118, 1291-1301
93. McCartney, B. M., Kulikauskas, R. M., LaJeunesse, D. R. and Fehon, R. G. (2000) The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. Development 127, 1315-1324
94. Pellock, B. J., Buff, E., White, K. and Hariharan, I. K. (2007) The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling. Dev. Biol. 304, 102-115
95. Zeng, Q. and Hong, W. (2008) The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals. Cancer Cell 13, 188-192
96. Badouel, C., Gardano, L., Amin, N., Garg, A., Rosenfeld, R., Le Bihan, T. and McNeill, H. (2009) The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie. Dev. Cell 16, 411-420
97. Chen, H. I., Einbond, A., Kwak, S. J., Linn, H., Koepf, E., Peterson, S., Kelly, J. W. and Sudol, M. (1997) Characterization of the WW domain of human yes-associated protein and its polyproline-containing ligands. J. Biol. Chem. 272, 17070-17077
98. Kasanov, J., Pirozzi, G., Uveges, A. J. and Kay, B. K. (2001) Characterizing Class I WW domains defines key specificity determinants and generates mutant domains with novel specificities. Chem. Biol. 8, 231-241
99. Pires, J. R., Taha-Nejad, F., Toepert, F., Ast, T., Hoffmuller, U., Schneider-Mergener, J., Kuhne, R., Macias, M. J. and Oschkinat, H. (2001) Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope. J. Mol. Biol. 314, 1147-1156
100. Zhao, B., Li, L., Lu, Q., Wang, L. H., Liu, C. Y., Lei, Q. and Guan, K. L. (2011) Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 25, 51-63
101. Skouloudaki, K. and Walz, G. (2012) YAP1 recruits c-Abl to protect angiomotin-like 1 from Nedd4-mediated degradation. PLoS ONE 7, e35735
102. Chan, S. W., Lim, C. J., Chong, Y. F., Pobbati, A. V., Huang, C. and Hong, W. (2011) Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J. Biol. Chem. 286, 7018-7026
103. Yin, M. and Zhang, L. (2011) Hippo signaling: a hub of growth control, tumor suppression and pluripotency maintenance. J. Genet. Genomics 38, 471-481
104. Liu, X., Yang, N., Figel, S. A., Wilson, K. E., Morrison, C. D., Gelman, I. H. and Zhang, J. (2013) PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 32, 1266-1273
105. Wang, W., Huang, J., Wang, X., Yuan, J., Li, X., Feng, L., Park, J. I. and Chen, J. (2012) PTPN14 is required for the density-dependent control of YAP1. Genes Dev. 26, 1959-1971
106. Harvey, K. and Tapon, N. (2007) The Salvador-Warts-Hippo pathway: an emerging tumour-suppressor network. Nat. Rev. Cancer 7, 182-191
107. Pan, D. (2010) The hippo signaling pathway in development and cancer. Dev. Cell 19, 491-505
108. Baumgartner, R., Poernbacher, I., Buser, N., Hafen, E. and Stocker, H. (2010) The WW domain protein Kibra acts upstream of Hippo in Drosophila . Dev. Cell 18, 309-316
109. Yu, J., Zheng, Y., Dong, J., Klusza, S., Deng, W. M. and Pan, D. (2010) Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev. Cell 18, 288-299
110. Moleirinho, S., Chang, N., Sims, A. H., Tilston-Lünel, A. M., Angus, L., Steele, A., Boswell, V., Barnett, S. C., Ormandy, C., Faratian, D. et al. (2012) KIBRA exhibits MST-independent functional regulation of the Hippo signaling pathway in mammals. Oncogene, doi:10.1038/onc.2012.196
111. Xiao, L., Chen, Y., Ji, M. and Dong, J. (2011) KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J. Biol. Chem. 286, 7788-7796
112. Visser-Grieve, S., Hao, Y. and Yang, X. (2012) Human homolog of Drosophila expanded, hEx, functions as a putative tumor suppressor in human cancer cell lines independently of the Hippo pathway. Oncogene 31, 1189-1195
113. Ishiuchi, T. and Takeichi, M. (2011) Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nat. Cell Biol. 13, 860-866
114. Ishiuchi, T. and Takeichi, M. (2012) Nectins localize Willin to cell-cell junctions. Genes Cells 17, 387-397
115. Ling, C., Zheng, Y., Yin, F., Yu, J., Huang, J., Hong, Y., Wu, S. and Pan, D. (2010) The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded. Proc. Natl. Acad. Sci. U.S.A. 107, 10532-10537
116. Robinson, B. S., Huang, J., Hong, Y. and Moberg, K. H. (2010) Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr. Biol. 20, 582-590
117. Chen, C. L., Gajewski, K. M., Hamaratoglu, F., Bossuyt, W., Sansores-Garcia, L., Tao, C. and Halder, G. (2010) The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila . Proc. Natl. Acad. Sci. U.S.A. 107, 15810-15815
118. Silva, E., Tsatskis, Y., Gardano, L., Tapon, N. and McNeill, H. (2006) The tumor-suppressor gene fat controls tissue growth upstream of expanded in the hippo signaling pathway. Curr. Biol. 16, 2081-2089
119. Willecke, M., Hamaratoglu, F., Kango-Singh, M., Udan, R., Chen, C. L., Tao, C., Zhang, X. and Halder, G. (2006) The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. Curr. Biol. 16, 2090-2100
120. Bennett, F. C. and Harvey, K. F. (2006) Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101-2110
121. Cho, E., Feng, Y., Rauskolb, C., Maitra, S., Fehon, R. and Irvine, K. D. (2006) Delineation of a Fat tumor suppressor pathway. Nat. Genet. 38, 1142-1150
122. Ungvari, I., Hullam, G., Antal, P., Kiszel, P. S., Gezsi, A., Hadadi, E., Virag, V., Hajos, G., Millinghoffer, A., Nagy, A. et al. (2012) Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance. PLoS ONE 7, e33573
123. Hong, M. G., Reynolds, C. A., Feldman, A. L., Kallin, M., Lambert, J. C., Amouyel, P., Ingelsson, E., Pedersen, N. L. and Prince, J. A. (2012) Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease. Hum. Mutat. 33, 521-529
124. Potkin, S. G., Guffanti, G., Lakatos, A., Turner, J. A., Kruggel, F., Fallon, J. H., Saykin, A. J., Orro, A., Lupoli, S., Salvi, E. et al. (2009) Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease. PLoS ONE 4, e6501
125. Stein, J. L., Hua, X., Lee, S., Ho, A. J., Leow, A. D., Toga, A. W., Saykin, A. J., Shen, L., Foroud, T., Pankratz, N. et al. (2010) Voxelwise genome-wide association study (vGWAS). Neuroimage 53, 1160-1174
126. Shen, C. and Kaelin, Jr, W. G. (2013) The VHL/HIF axis in clear cell renal carcinoma. Semin. Cancer Biol. 23, 18-25
127. Buffart, T. E., Carvalho, B., van Grieken, N. C., van Wieringen, W. N., Tijssen, M., Kranenbarg, E. M., Verheul, H. M., Grabsch, H. I., Ylstra, B., van de Velde, C. J. and Meijer, G. A. (2012) Losses of chromosome 5q and 14q are associated with favorable clinical outcome of patients with gastric cancer. Oncologist 17, 653-662
128. Bowden, W., Skorupski, J., Kovanci, E. and Rajkovic, A. (2009) Detection of novel copy number variants in uterine leiomyomas using high-resolution SNP arrays. Mol. Hum. Reprod. 15, 563-568
129. Perez-Magan, E., Rodriguez de Lope, A., Ribalta, T., Ruano, Y., Campos-Martin, Y., Perez-Bautista, G., Garcia, J. F., Garcia-Claver, A., Fiano, C., Hernandez-Moneo, J. L. et al. (2010) Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas. Neuro-Oncology 12, 1278-1290
130. Alahmadi, H. and Croul, S. E. (2011) Pathology and genetics of meningiomas. Semin. Diagn. Pathol. 28, 314-324
131. Dahlback, H. S., Brandal, P., Gorunova, L., Widing, E., Meling, T. R., Krossnes, B. K. and Heim, S. (2011) Genomic aberrations in pediatric gliomas and embryonal tumors. Genes Chromosomes Cancer 50, 788-799
132. Dichamp, C., Taillibert, S., Aguirre-Cruz, L., Lejeune, J., Marie, Y., Kujas, M., Delattre, J. Y., Hoang-Xuan, K. and Sanson, M. (2004) Loss of 14q chromosome in oligodendroglial and astrocytic tumors. J. Neuro-Oncol. 67, 281-285
133. Volchenboum, S. L., Li, C., Li, S., Attiyeh, E. F., Reynolds, C. P., Maris, J. M., Look, A. T. and George, R. E. (2009) Comparison of primary neuroblastoma tumors and derivative early-passage cell lines using genome-wide single nucleotide polymorphism array analysis. Cancer Res. 69, 4143-4149
134. Pelz, A. F., Agaimy, A., Daniels, M., Evert, M., Schulz, H. U., Luders, P., Muller, G., Lasota, J., Ropke, A., Wieacker, P. et al. (2011) Gastrointestinal stromal tumor presenting as a rectovaginal mass. Clinicopathologic and molecular-genetic characterization of a rare tumor with a literature review. Hum. Pathol. 42, 586-593
135. Ylipaa, A., Hunt, K. K., Yang, J., Lazar, A. J., Torres, K. E., Lev, D. C., Nykter, M., Pollock, R. E., Trent, J. and Zhang, W. (2011) Integrative genomic characterization and a genomic staging system for gastrointestinal stromal tumors. Cancer 117, 380-389
136. Alexiou, G. A., Markoula, S., Gogou, P. and Kyritsis, A. P. (2011) Genetic and molecular alterations in meningiomas. Clin. Neurol. Neurosurg. 113, 261-267
137. Yamamoto, H., Tobo, T., Nakamori, M., Imamura, M., Kojima, A., Oda, Y., Nakamura, N., Takahira, T., Yao, T. and Tsuneyoshi, M. (2009) Neurofibromatosis type 1-related gastrointestinal stromal tumors: a special reference to loss of heterozygosity at 14q and 22q. J. Cancer Res. Clin. Oncol. 135, 791-798
138. Tarpey, P., Thomas, S., Sarvananthan, N., Mallya, U., Lisgo, S., Talbot, C. J., Roberts, E. O., Awan, M., Surendran, M., McLean, R. J. et al. (2006) Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat. Genet. 38, 1242-1244