| First Author | Yi C | Year | 2011 |
| Journal | Cancer Cell | Volume | 19 |
| Issue | 4 | Pages | 527-40 |
| PubMed ID | 21481793 | Mgi Jnum | J:170978 |
| Mgi Id | MGI:4948164 | Doi | 10.1016/j.ccr.2011.02.017 |
| Citation | Yi C, et al. (2011) A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin's Regulation of Mitogenic Signaling and Tumor Suppressive Functions. Cancer Cell 19(4):527-40 |
| abstractText | The Merlin/NF2 tumor suppressor restrains cell growth and tumorigenesis by controlling contact-dependent inhibition of proliferation. We have identified a tight-junction-associated protein complex comprising Merlin, Angiomotin, Patj, and Pals1. We demonstrate that Angiomotin functions downstream of Merlin and upstream of Rich1, a small GTPase Activating Protein, as a positive regulator of Rac1. Merlin, through competitive binding to Angiomotin, releases Rich1 from the Angiomotin-inhibitory complex, allowing Rich1 to inactivate Rac1, ultimately leading to attenuation of Rac1 and Ras-MAPK pathways. Patient-derived Merlin mutants show diminished binding capacities to Angiomotin and are unable to dissociate Rich1 from Angiomotin or inhibit MAPK signaling. Depletion of Angiomotin in Nf2(-/-) Schwann cells attenuates the Ras-MAPK signaling pathway, impedes cellular proliferation in vitro and tumorigenesis in vivo. |
