Video Experimental Relacionado
Updated: Jul 31, 2026
12:57
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
La subfamilia de la proteína quinasa activada por el estrés de las cinasas c-Jun
J M Kyriakis1, P Banerjee, E Nikolakaki
1Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, Charlestown 02129.
Nature
|May 12, 1994
Resumen
Las proteínacinasas activadas por estrés (SAPK) son una nueva clase de MAP. Estas quinasas son activadas por el estrés celular y el factor de necrosis tumoral alfa, regulando la actividad de c-Jun.
Área de la Ciencia:
- Las vías de señalización celular.
- Biología molecular La biología molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las kinasas de proteínas activadas por mitógenos (MAP) Erk-1 y Erk-2 son kinasas dirigidas por prolina activadas por la fosforilación de tirosina y treonina.
- La quinasa p54, similar a Erks-1/2, está dirigida a la prolina y requiere fosforilación de Tyr y Ser/Thr para su actividad.
- p54 exhibe una distinta especificidad de sustrato, fosforilando el dominio de transactivación c-Jun más activamente que el pp90rsk.
Objetivo del estudio:
- Para caracterizar la quinasa p54 y su subfamilia de quinasas reguladas extracelularmente.
- Investigar los mecanismos de activación y las vías de señalización que involucran a p54.
- Establecer el papel de la p54 en las respuestas al estrés celular y la señalización del TNF-alfa.
Principales métodos:
- La clonación molecular de la p54.
- Análisis de la actividad de la quinasa y la especificidad del sustrato.
- Investigación de la activación por mitógenos, ésteres de forbol, estrés celular y factor de necrosis tumoral (TNF) -alfa.
Principales resultados:
- La clonación molecular reveló que p54 pertenece a una subfamilia única de quinasas reguladas extracelularmente, denominadas proteína quinasa activada por estrés (SAPK).
- Los SAPK son idénticos en un 40-45% a los Erks-1/2 pero están poco activados por los mitógenos o los ésteres de forbol.
- Las SAPK son las principales quinasas c-Jun N-terminales activadas por el estrés celular y el TNF-alfa, y también por la esfingomielinasa.
Conclusiones:
- Las SAPKs definen una nueva vía de señalización activada por el TNF-alfa y el estrés celular.
- Esta vía puede ser iniciada por un segundo mensajero basado en la esfingomielina.
- Las SAPK juegan un papel crucial en la regulación de la actividad de c-Jun en respuesta al estrés y el TNF-alfa.
Videos de Conceptos Relacionados
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:07MAPK Signaling Cascades
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...
01:20The JAK-STAT Signaling Pathway
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...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...