A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin's Regulation of Mitogenic Signaling and Tumor Suppressive Functions

Cancer Cell

Volumn 19, Issue 4, 2011, Pages 527-540

  Yi, Chunling ^a   Troutman, Scott ^a   Fera, Daniela ^a,b   Stemmer Rachamimov, Anat ^c   Avila, Jacqueline L ^a   Christian, Neepa ^a   Persson, Nathalie Luna ^d   Shimono, Akihiko ^e   Speicher, David W ^a   Marmorstein, Ronen ^a,b   Holmgren, Lars ^d   Kissil, Joseph L ^a  

^a WISTAR INSTITUTE   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d KAROLINSKA INSTITUTE   (Sweden)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOMOTIN; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; MEMBRANE PROTEIN; MERLIN; MITOGEN ACTIVATED PROTEIN KINASE; PALS1 PROTEIN; PATJ PROTEIN; RAC1 PROTEIN; RAS PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CANCER MODEL; CONTROLLED STUDY; HUMAN; HUMAN CELL; MOUSE; NEURILEMOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SCHWANN CELL; SIGNAL TRANSDUCTION; TIGHT JUNCTION;

EID: 79953753962     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2011.02.017     Document Type: Article

References (44)

1. Alfthan K., Heiska L., Gronholm M., Renkema G.H., Carpen O. Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization. J. Biol. Chem. 2004, 279:18559-18566.
2. Ammoun S., Flaiz C., Ristic N., Schuldt J., Hanemann C.O. Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-regulated kinase pathway in human schwannoma. Cancer Res. 2008, 68:5236-5245.
3. Beeser A., Jaffer Z.M., Hofmann C., Chernoff J. Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors. J. Biol. Chem. 2005, 280:36609-36615.
4. Benhamouche S., Curto M., Saotome I., Gladden A.B., Liu C.H., Giovannini M., McClatchey A.I. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 2010, 24:1718-1730.
5. Curto M., Cole B.K., Lallemand D., Liu C.H., McClatchey A.I. Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J. Cell Biol. 2007, 177:893-903.
6. Dalgliesh G.L., Furge K., Greenman C., Chen L., Bignell G., Butler A., Davies H., Edkins S., Hardy C., Latimer C., et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 2010, 463:360-363.
7. Deguen B., Goutebroze L., Giovannini M., Boisson C., van der Neut R., Jaurand M.C., Thomas G. Heterogeneity of mesothelioma cell lines as defined by altered genomic structure and expression of the NF2 gene. Int. J. Cancer 1998, 77:554-560.
8. Ernkvist M., Birot O., Sinha I., Veitonmaki N., Nystrom S., Aase K., Holmgren L. Differential roles of p80- and p130-angiomotin in the switch between migration and stabilization of endothelial cells. Biochim. Biophys. Acta 2008, 1783:429-437.
9. Ernkvist M., Luna Persson N., Audebert S., Lecine P., Sinha I., Liu M., Schlueter M., Horowitz A., Aase K., Weide T., et al. The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood 2009, 113:244-253.
10. Forster C. Tight junctions and the modulation of barrier function in disease. Histochem. Cell Biol. 2008, 130:55-70.
11. Furuta B., Harada A., Kobayashi Y., Takeuchi K., Kobayashi T., Umeda M. Identification and functional characterization of nadrin variants, a novel family of GTPase activating protein for rho GTPases. J. Neurochem. 2002, 82:1018-1028.
12. Giovannini M., Robanus-Maandag E., van der Valk M., Niwa-Kawakita M., Abramowski V., Goutebroze L., Woodruff J.M., Berns A., Thomas G. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev. 2000, 14:1617-1630.
13. Hanemann C.O. Magic but treatable? Tumours due to loss of merlin. Brain 2008, 131:606-615.
14. Harada A., Furuta B., Takeuchi K., Itakura M., Takahashi M., Umeda M. Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated exocytosis. J. Biol. Chem. 2000, 275:36885-36891.
15. Hennigan R.F., Foster L.A., Chaiken M.F., Mani T., Gomes M.M., Herr A.B., Ip W. Fluorescence resonance energy transfer analysis of merlin conformational changes. Mol. Cell. Biol. 2010, 30:54-67.
16. Hirokawa Y., Tikoo A., Huynh J., Utermark T., Hanemann C.O., Giovannini M., Xiao G.H., Testa J.R., Wood J., Maruta H. A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor. Cancer J. 2004, 10:20-26.
17. Iden S., Collard J.G. Crosstalk between small GTPases and polarity proteins in cell polarization. Nat. Rev. Mol. Cell Biol. 2008, 9:846-859.
18. Jin H., Sperka T., Herrlich P., Morrison H. Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase. Nature 2006, 442:576-579.
19. Kaempchen K., Mielke K., Utermark T., Langmesser S., Hanemann C.O. Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells. Hum. Mol. Genet. 2003, 12:1211-1221.
20. Kalamarides M., Niwa-Kawakita M., Leblois H., Abramowski V., Perricaudet M., Janin A., Thomas G., Gutmann D.H., Giovannini M. Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse. Genes Dev. 2002, 16:1060-1065.
21. Kissil J.L., Johnson K.C., Eckman M.S., Jacks T. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J. Biol. Chem. 2002, 277:10394-10399.
22. Kissil J.L., Wilker E.W., Johnson K.C., Eckman M.S., Yaffe M.B., Jacks T. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol. Cell 2003, 12:841-849.
23. Lallemand D., Curto M., Saotome I., Giovannini M., McClatchey A.I. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev. 2003, 17:1090-1100.
24. Lallemand D., Manent J., Couvelard A., Watilliaux A., Siena M., Chareyre F., Lampin A., Niwa-Kawakita M., Kalamarides M., Giovannini M. Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas. Oncogene 2009, 28:854-865.
25. Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., Ishii R., Giovannini M., Hanemann C.O., Long S.B., et al. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 2010, 140:477-490.
26. Maitra S., Kulikauskas R.M., Gavilan H., Fehon R.G. The tumor suppressors Merlin and expanded function cooperatively to modulate receptor endocytosis and signaling. Curr. Biol. 2006, 16:702-709.
27. Miyoshi J., Takai Y. Molecular perspective on tight-junction assembly and epithelial polarity. Adv. Drug Deliv. Rev. 2005, 57:815-855.
28. Morris Z.S., McClatchey A.I. Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma. Proc. Natl. Acad. Sci. USA 2009, 106:9767-9772.
29. Morrison H., Sperka T., Manent J., Giovannini M., Ponta H., Herrlich P. Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res. 2007, 67:520-527.
30. Okada T., Lopez-Lago M., Giancotti F.G. Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane. J. Cell Biol. 2005, 171:361-371.
31. Ramesh V. Merlin and the ERM proteins in Schwann cells, neurons and growth cones. Nat. Rev. Neurosci. 2004, 5:462-470.
32. Richnau N., Aspenstrom P. Rich, a rho GTPase-activating protein domain-containing protein involved in signaling by Cdc42 and Rac1. J. Biol. Chem. 2001, 276:35060-35070.
33. Rong R., Surace E.I., Haipek C.A., Gutmann D.H., Ye K. Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression. Oncogene 2004, 23:8447-8454.
34. Schulz A., Geissler K.J., Kumar S., Leichsenring G., Morrison H., Baader S.L. Merlin inhibits neurite outgrowth in the CNS. J. Neurosci. 2010, 30:10177-10186.
35. Shaw R.J., Paez J.G., Curto M., Yaktine A., Pruitt W.M., Saotome I., O'Bryan J.P., Gupta V., Ratner N., Der C.J., et al. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev. Cell 2001, 1:63-72.
36. Stokowski R.P., Cox D.R. Functional analysis of the neurofibromatosis type 2 protein by means of disease-causing point mutations. Am. J. Hum. Genet. 2000, 66:873-891.
37. Sugihara-Mizuno Y., Adachi M., Kobayashi Y., Hamazaki Y., Nishimura M., Imai T., Furuse M., Tsukita S. Molecular characterization of angiomotin/JEAP family proteins: interaction with MUPP1/Patj and their endogenous properties. Genes Cells 2007, 12:473-486.
38. Wells C.D., Fawcett J.P., Traweger A., Yamanaka Y., Goudreault M., Elder K., Kulkarni S., Gish G., Virag C., Lim C., et al. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 2006, 125:535-548.
39. Wong H.K., Lahdenranta J., Kamoun W.S., Chan A.W., McClatchey A.I., Plotkin S.R., Jain R.K., di Tomaso E. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res. 2010, 70:3483-3493.
40. Xiao G.H., Beeser A., Chernoff J., Testa J.R. p21-activated kinase links Rac/Cdc42 signaling to merlin. J. Biol. Chem. 2002, 277:883-886.
41. Xiao G.H., Gallagher R., Shetler J., Skele K., Altomare D.A., Pestell R.G., Jhanwar S., Testa J.R. The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression. Mol. Cell. Biol. 2005, 25:2384-2394.
42. Yi C., Kissil J.L. Merlin in organ size control and tumorigenesis: Hippo versus EGFR?. Genes Dev. 2010, 24:1673-1679.
43. Yi C., Wilker E.W., Yaffe M.B., Stemmer-Rachamimov A., Kissil J.L. Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2. Cancer Res. 2008, 68:7932-7937.
44. Zhang N., Bai H., David K.K., Dong J., Zheng Y., Cai J., Giovannini M., Liu P., Anders R.A., Pan D. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 2010, 19:27-38.