Video Experimental Relacionado
Updated: Apr 18, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
12.6K
La fosforilación de las proteínas adaptadoras inmunes innatas MAVS, STING y TRIF induce la activación de IRF3
Siqi Liu1, Xin Cai1, Jiaxi Wu1
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Science (New York, N.Y.)
|February 1, 2015
Resumen
El estudio revela que la fosforilación de las proteínas adaptadoras MAVS y STING es crucial para reclutar y activar el factor regulador del interferón 3 (IRF3), iniciando la respuesta antiviral del interferón de tipo I (IFN).
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Virología Virología.
Sus antecedentes:
- MAVS y STING son proteínas adaptadoras clave que envían señales desde los sensores de ácido nucleico citosólico RIG-I y cGAS.
- Esta vía de señalización es esencial para inducir interferones tipo I (IFN) y otras moléculas antivirales durante las infecciones virales.
Objetivo del estudio:
- Investigar el mecanismo por el cual MAVS y STING activan el factor regulador de interferón 3 (IRF3).
- Para aclarar el papel de la fosforilación en el reclutamiento y la activación de IRF3.3.
Principales métodos:
- Investigaron los sitios de fosforilación en MAVS y STING utilizando ensayos de quinasa.
- Se analizó la interacción entre los adaptadores fosforilados y el IRF3 a través de la coinmunoprecipitación.
- Estudió la activación de IRF3 por TBK1 quinasa en respuesta a la estimulación.
Principales resultados:
- MAVS y STING poseen grupos de serina y treonina conservados fosforilados por IKK y/o TBK1.
- Los MAVS y STING fosforilados se unen a una superficie cargada positivamente en IRF3, reclutándola para la fosforilación y activación mediadas por TBK1.
- TRIF, un adaptador de receptores de tipo Toll, también activa IRF3 a través de un mecanismo similar dependiente de la fosforilación.
Conclusiones:
- La fosforilación de las proteínas adaptadoras inmunes innatas es un mecanismo conservado para el reclutamiento selectivo de IRF3.
- Este reclutamiento dependiente de la fosforilación es esencial para activar la vía del interferón tipo I contra las infecciones virales.
Videos de Conceptos Relacionados
01:20The JAK-STAT Signaling Pathway
14.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
14.2K
01:07MAPK Signaling Cascades
9.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K
01:11IP3/DAG Signaling Pathway
16.2K
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...
16.2K
01:42Phosphoinositides and PIPs
11.8K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
11.8K
02:26NF-κB-dependent Signaling Pathway
10.9K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.9K
01:22PI3K/mTOR/AKT Signaling Pathway
6.5K
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...
6.5K