Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2257K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Curto, M. Articles by McClatchey, A. I. Search for Related Content PubMed PubMed Citation Articles by Curto, M. Articles by McClatchey, A. I. Related Collections Related Article Social Bookmarking                            What's this?

Contact-dependent inhibition of EGFR signaling by Nf2/Merlin

MGH Center for Cancer Research and Harvard Medical School Department of Pathology, Charlestown, MA 02129

Correspondence to Andrea I. McClatchey: mcclatch{at}helix.mgh.harvard.edu

The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a membrane/cytoskeleton-associated protein that mediates contact-dependent inhibition of proliferation. Here we show that upon cell–cell contact Merlin coordinates the processes of adherens junction stabilization and negative regulation of epidermal growth factor receptor (EGFR) signaling by restraining the EGFR into a membrane compartment from which it can neither signal nor be internalized. In confluent Nf2^–/– cells, EGFR activation persists, driving continued proliferation that is halted by specific EGFR inhibitors. These studies define a new mechanism of tumor suppression, provide mechanistic insight into the poorly understood phenomenon of contact-dependent inhibition of proliferation, and suggest a therapeutic strategy for NF2-mutant tumors.

Abbreviations used in this paper: AJ, adherens junction; EGFR, epidermal growth factor receptor; ERM, Ezrin/Radixin/Moesin; FERM, four-point-one, ERM; LDC, liver-derived epithelial cell; MEF, mouse embryo fibroblast; NF2, neurofibromatosis type 2; OB, osteoblast; pTyr, phosphotyrosine; RTK, receptor tyrosine kinase; Tr-EGF, Texas red–conjugated EGF.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Merlin casts spell on proliferation protein

Mitch Leslie
J. Cell Biol. 2007 177: 744a. [Full Text] [PDF]

This article has been cited by other articles:

• Kawada, K., Upadhyay, G., Ferandon, S., Janarthanan, S., Hall, M., Vilardaga, J.-P., Yajnik, V. (2009). Cell Migration Is Regulated by Platelet-Derived Growth Factor Receptor Endocytosis. Mol. Cell. Biol. 29: 4508-4518 [Abstract] [Full Text]  
• Evans, D. G., Kalamarides, M., Hunter-Schaedle, K., Blakeley, J., Allen, J., Babovic-Vuskanovic, D., Belzberg, A., Bollag, G., Chen, R., DiTomaso, E., Golfinos, J., Harris, G., Jacob, A., Kalpana, G., Karajannis, M., Korf, B., Kurzrock, R., Law, M., McClatchey, A., Packer, R., Roehm, P., Rubenstein, A., Slattery, W. III, Tonsgard, J. H., Welling, D. B., Widemann, B., Yohay, K., Giovannini, M. (2009). Consensus Recommendations to Accelerate Clinical Trials for Neurofibromatosis Type 2. Clin. Cancer Res. 15: 5032-5039 [Abstract] [Full Text]  
• Lopez-Lago, M. A., Okada, T., Murillo, M. M., Socci, N., Giancotti, F. G. (2009). Loss of the Tumor Suppressor Gene NF2, Encoding Merlin, Constitutively Activates Integrin-Dependent mTORC1 Signaling. Mol. Cell. Biol. 29: 4235-4249 [Abstract] [Full Text]  
• Kim, J.-H., Kushiro, K., Graham, N. A., Asthagiri, A. R. (2009). Tunable interplay between epidermal growth factor and cell-cell contact governs the spatial dynamics of epithelial growth. Proc. Natl. Acad. Sci. USA 106: 11149-11153 [Abstract] [Full Text]  
• Getsios, S., Simpson, C. L., Kojima, S.-i., Harmon, R., Sheu, L. J., Dusek, R. L., Cornwell, M., Green, K. J. (2009). Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. JCB 185: 1243-1258 [Abstract] [Full Text]  
• Morris, Z. S., McClatchey, A. I. (2009). Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma. Proc. Natl. Acad. Sci. USA 106: 9767-9772 [Abstract] [Full Text]  
• Houshmandi, S. S., Emnett, R. J., Giovannini, M., Gutmann, D. H. (2009). The Neurofibromatosis 2 Protein, Merlin, Regulates Glial Cell Growth in an ErbB2- and Src-Dependent Manner. Mol. Cell. Biol. 29: 1472-1486 [Abstract] [Full Text]  
• Kesarwala, A. H., Samrakandi, M. M., Piwnica-Worms, D. (2009). Proteasome Inhibition Blocks Ligand-Induced Dynamic Processing and Internalization of Epidermal Growth Factor Receptor via Altered Receptor Ubiquitination and Phosphorylation. Cancer Res. 69: 976-983 [Abstract] [Full Text]  
• Cole, B. K., Curto, M., Chan, A. W., McClatchey, A. I. (2008). Localization to the Cortical Cytoskeleton Is Necessary for Nf2/Merlin-Dependent Epidermal Growth Factor Receptor Silencing. Mol. Cell. Biol. 28: 1274-1284 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents