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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Interactions Between Signaling Pathways01:19

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Video Experimental Relacionado

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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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La vía de señalización del hipopótamo interactoma.

Young Kwon1, Arunachalam Vinayagam, Xiaoyun Sun

  • 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)
|October 12, 2013
PubMed
Resumen

Los investigadores mapearon las interacciones de proteínas de la vía del hipopótamo, identificando 153 proteínas y 204 interacciones. Se descubrió que una nueva proteína, Leash, degrada al Yorkie, lo que afecta el crecimiento de los órganos y el cáncer.

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Área de la Ciencia:

  • Biología celular Biología celular.
  • Biología del desarrollo Biología del desarrollo.
  • Biología molecular La biología molecular.

Sus antecedentes:

  • La vía de Hippo es crucial para regular el tamaño del órgano controlando la proliferación celular y la apoptosis.
  • A pesar de su importancia, la composición completa y la estructura de la vía de Hippo siguen siendo incompletamente comprendidas.

Objetivo del estudio:

  • Construir una red integral de interacción proteína-proteína (Hippo-PPIN) para la vía de la Drosophila Hippo.
  • Identificar nuevos componentes y mecanismos reguladores dentro de la vía de Hippo.

Principales métodos:

  • Utilizó la espectrometría de masas con los componentes existentes de la vía Hippo como cebos para generar el Hippo-PPIN.
  • Se empleó la interferencia de ARN (RNAi) para evaluar el impacto funcional de las proteínas identificadas en el coactivador transcripcional Yorkie (Yki).
  • Seleccionado y caracterizado un nuevo miembro de la familia alfa-arrestina, Leash.

Principales resultados:

  • Generó un Hippo-PPIN de alta confianza que comprende 153 proteínas y 204 interacciones.
  • El cribado de RNAi reveló que el agotamiento del 67% de las proteínas identificadas afecta la actividad de Yorkie (Yki) de manera positiva o negativa.
  • Se identificó a Leash como un nuevo regulador que promueve la degradación de Yorkie (Yki) a través de la vía lisosomal.

Conclusiones:

  • El Hippo-PPIN generado proporciona un recurso valioso para comprender la composición y la función de la vía Hippo.
  • La correa representa un componente recientemente descubierto que regula negativamente la vía del hipopótamo al dirigirse al Yorkie (Yki) para su degradación.
  • Esta investigación profundiza la comprensión del papel de la vía de Hippo en el crecimiento normal de los órganos y sus implicaciones en el desarrollo del cáncer.