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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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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.
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...
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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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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...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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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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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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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.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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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...
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JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
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Señalización AKT/PKB: navegación por la red

Brendan D Manning1, Alex Toker2

  • 1Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Cell
|April 22, 2017
PubMed
Resumen
Este resumen es generado por máquina.

La red de señalización AKT, también conocida como proteína quinasa B (PKB), es crucial en biología celular y medicina. Comprender su compleja regulación y funciones es vital para abordar enfermedades como el cáncer y la diabetes.

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Área de la Ciencia:

  • La bioquímica
  • Biología celular
  • La medicina molecular

Sus antecedentes:

  • La serina/treonina quinasa AKT (proteína quinasa B) ha sido ampliamente estudiada durante 25 años.
  • Los avances incluyen la comprensión de sus reguladores aguas arriba, efectores aguas abajo (GSK3, FoxO, mTORC1) y red de señalización compleja.
  • La red AKT está ubicua en las células y desempeña funciones fisiológicas en todos los sistemas de órganos.

Objetivo del estudio:

  • Revisar el amplio conocimiento de la señalización AKT.
  • Destacar la importancia de la TCA en diversas enfermedades y el desarrollo terapéutico.

Principales métodos:

  • Revisión de la literatura existente y estudios genéticos (en ratones y en humanos).
  • Análisis de las entradas reguladoras de AKT, nodos de señalización aguas abajo y circuitos de red.
  • Examen del papel de AKT en diversas condiciones patológicas.

Principales resultados:

  • Se han logrado avances significativos en la comprensión de la regulación de AKT y sus vías de señalización aguas abajo.
  • La disfunción AKT está implicada en numerosas enfermedades, incluidos el cáncer, la diabetes y los trastornos neurológicos.
  • El desarrollo de inhibidores de moléculas pequeñas selectivos de AKT muestra una promesa terapéutica.

Conclusiones:

  • La comprensión integral de la red de señalización AKT es fundamental para la investigación biomédica.
  • La desregulación de la vía AKT contribuye a una amplia gama de enfermedades humanas.
  • La investigación continua en la señalización de AKT impacta en múltiples disciplinas científicas y estrategias terapéuticas.