Your browser doesn't support javascript.
loading
DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2.
Kwan, Julian; Sczaniecka, Anna; Heidary Arash, Emad; Nguyen, Liem; Chen, Chia-Chun; Ratkovic, Srdjana; Klezovitch, Olga; Attisano, Liliana; McNeill, Helen; Emili, Andrew; Vasioukhin, Valeri.
Afiliación
  • Kwan J; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Sczaniecka A; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Heidary Arash E; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Nguyen L; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Chen CC; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • Ratkovic S; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Klezovitch O; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Attisano L; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • McNeill H; Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
  • Emili A; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Vasioukhin V; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Genes Dev ; 30(24): 2696-2709, 2016 12 15.
Article en En | MEDLINE | ID: mdl-28087714
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation. Affinity purification/mass spectrometry revealed a critical role of DLG5 in the formation of protein assemblies containing core Hippo kinases mammalian ste20 homologs 1/2 (MST1/2) and Par-1 polarity proteins microtubule affinity-regulating kinases 1/2/3 (MARK1/2/3). Consistent with this finding, Hippo signaling is markedly hyperactive in mammalian Dlg5-/- tissues and cells in vivo and ex vivo and in Drosophila upon dlg5 knockdown. Conditional deletion of Mst1/2 fully rescued the phenotypes of brain-specific Dlg5 knockout mice. Dlg5 also interacts genetically with Hippo effectors Yap1/Taz Mechanistically, we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (LATS1/2), uses its scaffolding function to link MST1/2 with MARK3, and inhibits MST1/2 kinase activity. These data reveal a direct connection between cell polarity proteins and Hippo, which is essential for proper development of multicellular organisms.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Polaridad Celular / Proteínas Serina-Treonina Quinasas / Regulación del Desarrollo de la Expresión Génica / Proteínas Supresoras de Tumor / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Polaridad Celular / Proteínas Serina-Treonina Quinasas / Regulación del Desarrollo de la Expresión Génica / Proteínas Supresoras de Tumor / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos