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The JAK-STAT Signaling Pathway

The 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...

Amplifying Signals via Enzymatic Cascade

Amplifying Signals via Enzymatic Cascade

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...

Interactions Between Signaling Pathways

Interactions 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...

MAPK Signaling Cascades

MAPK 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...

Intracellular Signaling Cascades

Intracellular Signaling Cascades

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...

Notch Signaling Pathway

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...

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Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells

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SnapShot: Jak-STAT señalización II

Alejandro V Villarino¹, Massimo Gadina¹, John J O'Shea¹

¹National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

|June 27, 2020

Resumen

La vía Janus kinase- (JAK) y el transductor de señal de transcripción (STAT) permiten una rápida comunicación celular. Los descubrimientos han llevado a los inhibidores de JAK (Jakinibs) para el tratamiento de trastornos inmunes, autoinmunes y de la sangre.

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Área de la Ciencia:

Biología molecular
Inmunología
Farmacología

Sus antecedentes:

La vía de Janus kinase- (JAK) y el transductor de señal de transcripción (STAT) es un mecanismo de señalización crucial.
Median la comunicación rápida de los receptores celulares al núcleo, controlando la transcripción de genes.

Objetivo del estudio:

Para resaltar la importancia de la vía JAK-STAT en la señalización celular.
Subrayar el impacto traslacional de la comprensión de esta vía en el desarrollo de enfermedades y medicamentos.

Principales métodos:

Este estudio es una revisión de la investigación existente sobre la vía JAK-STAT.
Sintetiza los hallazgos de estudios genéticos, celulares y clínicos.

Principales resultados:

La vía JAK-STAT es fundamental para las respuestas celulares y la homeostasis.
La desregulación de esta vía está implicada en varias enfermedades, incluidas las inmunodeficiencias primarias, los trastornos autoinmunes y los cánceres.

Conclusiones:

La comprensión de la vía JAK-STAT ha revelado su papel en numerosas enfermedades.
Este conocimiento ha llevado directamente al desarrollo de una nueva clase de terapéuticos, los inhibidores de JAK (Jakinibs).