Video Experimental Relacionado
Updated: Jun 10, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
La fosforilación y la inactivación funcional de TSC2 por Erk tiene implicaciones para la esclerosis tuberosa y la
Li Ma1, Zhenbang Chen, Hediye Erdjument-Bromage
1Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cell
|April 27, 2005
Resumen
La quinasa regulada por la señal extracelular (Erk) inactiva el TSC2 a través de la fosforilación, promoviendo el crecimiento tumoral en el complejo de esclerosis tuberosa (TSC). El bloqueo de Erk Erk.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- El complejo de esclerosis tuberosa (TSC) es un trastorno genético caracterizado por la formación de tumores, causada por mutaciones en los genes TSC1 o TSC2.
- La tumorigénesis en el TSC no siempre implica pérdida de heterocigosidad (LOH).
- Se ha observado la activación de la quinasa regulada por la señal extracelular (Erk) en lesiones del TSC sin LOH.
Objetivo del estudio:
- Para investigar el papel de Erk en la tumorigénesis del TSC.
- Aclarar el mecanismo por el cual Erk influye en la función TSC2 y la señalización mTOR.
Principales métodos:
- Investigando la fosforilación dependiente de Erk del TSC2.2.
- Analizando la disociación del complejo TSC1-TSC2.
- Evaluación del impacto de la fosforilación TSC2 en la señalización mTOR y la proliferación celular.
- Utilizando un mutante TSC2 no fosforilable en las células tumorales TSC2+/- con activación Erk constitutiva.
Principales resultados:
- La fosforilación dependiente de Erk conduce a la disociación del TSC1-TSC2.
- El TSC2 fosforilado exhibe una inhibición deteriorada de la señalización mTOR, la proliferación celular y la transformación oncogénica.
- La expresión de un mutante TSC2 no fosforilable bloqueó la formación de tumores in vivo, mientras que el TSC2 de tipo salvaje no lo hizo.
Conclusiones:
- La vía Ras/MAPK, específicamente Erk, actúa aguas arriba del complejo TSC.
- Erk modula la señalización mTOR y contribuye a la progresión de la TSC a través de la fosforilación y la inactivación de la TSC2.
- Targeting Erk puede ofrecer una estrategia terapéutica para el TSC.
Videos de Conceptos Relacionados
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
01:22PI3K/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 rapamycin-insensitive companion...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...