La señalización alternativa Wnt activa el YAP/TAZ

Hyun Woo Park1, Young Chul Kim2, Bo Yu3

  • 1Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.

Cell
|August 16, 2015
PubMed
Resumen

Los coactivadores transcripcionales YAP y TAZ son reguladores clave del tamaño de los órganos y la homeostasis de los tejidos, y su desregulación contribuye al cáncer humano. Aquí, descubrimos YAP / TAZ como efectores de buena fe aguas abajo de la vía de señalización Wnt alternativa. Wnt5a/b y Wnt3a inducen la activación de YAP/TAZ independientemente de la señalización canónica de Wnt/β-catenina. Mecanísticamente, delineamos el "eje de señalización alternativo Wnt-YAP/TAZ" que consiste en Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2 para promover la activación de YAP/TAZ y la transcripción mediada por TEAD. YAP/TAZ median las funciones biológicas de la señalización Wnt alternativa, incluida la expresión génica, la diferenciación osteogénica, la migración celular y el antagonismo de la señalización Wnt/β-catenina. Juntos, nuestro trabajo establece a YAP/TAZ como mediadores críticos de la señalización alternativa de Wnt.

Videos de Conceptos Relacionados

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
11.0K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

2.6K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.6K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

1.9K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
6.4K