Cancer cell, 2011-04, Vol.19 (4), p.527-540
2011
Details
- Autor(en) / Beteiligte
- Titel
- A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin's Regulation of Mitogenic Signaling and Tumor Suppressive Functions
- Ist Teil von
- Cancer cell, 2011-04, Vol.19 (4), p.527-540
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. ► Merlin forms a tight-junction associated complex with Angiomotin, Patj, and Pals1 ► Merlin negatively regulates Rac1 by interfering with Rich1/Angiomotin interaction ► Merlin modulates MAPK signaling through the Rac1-Pak axis ► Angiomotin is required for tumorigenesis subsequent to loss of NF2
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108, 1878-3686eISSN: 1878-3686DOI: 10.1016/j.ccr.2011.02.017Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_122364559
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Cell Proliferation, GTPase-Activating Proteins - physiology, Humans, Intercellular Signaling Peptides and Proteins - physiology, MAP Kinase Signaling System, Medicin och hälsovetenskap, Membrane Proteins - physiology, Mice, Mice, SCID, Microfilament Proteins - physiology, Molecular Sequence Data, Neurofibromin 2 - physiology, Nucleoside-Phosphate Kinase - physiology, Peripheral Nerves - chemistry, rac1 GTP-Binding Protein - physiology, Schwann Cells - chemistry, Signal Transduction - physiology, Tight Junction Proteins, Tight Junctions - physiology, Tumor Suppressor Proteins - physiology