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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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The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Video Experimental Relacionado

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Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay
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Percepción combinada de señales en la vía BMP

Yaron E Antebi1, James M Linton1, Heidi Klumpe2

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Cell
|September 9, 2017
PubMed
Resumen

La vía de la proteína morfogenética ósea (BMP) utiliza combinaciones de ligandos para el procesamiento sofisticado de señales. Las células pueden realizar cálculos como la detección de la relación y el equilibrio mediante la alteración de la expresión del receptor.

Palabras clave:
Las BMPEl SMADProteína morfogenética óseamultiplicidadInteracciones entre los receptores de promiscuidad y los ligandosPercepción de la señalProcesamiento de señalesvías de señalización

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Área de la Ciencia:

  • Señales celulares
  • Biología molecular
  • La bioquímica

Sus antecedentes:

  • La señalización de la proteína morfogénica ósea (BMP) implica interacciones promiscuas entre múltiples ligandos y receptores.
  • La importancia funcional de estas interacciones complejas para el procesamiento de señales no ha sido clara, a menudo atribuida a la redundancia o la flexibilidad.

Objetivo del estudio:

  • Para aclarar las capacidades de procesamiento de señales de la vía BMP que surgen de las entradas multiligando.
  • Comprender cómo las interacciones competitivas receptor-ligando contribuyen a los cálculos celulares específicos.
  • Explorar cómo las células pueden modular estos cálculos a través de la expresión de receptores alternativos.

Principales métodos:

  • Análisis de las interacciones competitivas receptor-ligando dentro de la vía BMP.
  • Modelado de cálculos de procesamiento de señales basados en niveles relativos de ligando.
  • Investigación de la selección celular de las computaciones a través de la expresión de variantes de receptores alternativos.

Principales resultados:

  • La vía BMP realiza cálculos específicos en las entradas de multiligando, incluida la detección ratiométrica, la detección de equilibrio y la detección de desequilibrio.
  • Estos cálculos se derivan directamente de las interacciones competitivas entre los ligandos y los receptores.
  • Las células pueden seleccionar dinámicamente diferentes estrategias computacionales mediante la expresión de distintas variantes de receptores.

Conclusiones:

  • Las interacciones promiscua receptor-ligando en la vía BMP tienen un papel directo en el procesamiento de señales, permitiendo el control celular cuantitativo.
  • Los hallazgos establecen principios operativos para controlar las respuestas celulares utilizando ligandos BMP.
  • Principios similares de procesamiento de señales pueden aplicarse a otras vías de señalización promiscuas.