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Related Concept Videos

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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Amplifying Signals via Enzymatic Cascade01:22

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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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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
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MAPK Signaling Cascades01:07

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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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Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

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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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Notch Signaling Pathway03:14

Notch Signaling Pathway

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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.
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Time-resolved F&#246;rster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
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SnapShot: Jak-STAT Signaling 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.

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Summary

The Janus kinase- (JAK) and signal transducer of transcription (STAT) pathway enables rapid cell communication. Discoveries have led to JAK inhibitors (Jakinibs) for treating immune, autoimmune, and blood disorders.

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Area of Science:

  • Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • The Janus kinase- (JAK) and signal transducer of transcription (STAT) pathway is a crucial signaling mechanism.
  • It mediates rapid communication from cell receptors to the nucleus, controlling gene transcription.

Purpose of the Study:

  • To highlight the significance of the JAK-STAT pathway in cellular signaling.
  • To underscore the translational impact of understanding this pathway in disease and drug development.

Main Methods:

  • This study is a review of existing research on the JAK-STAT pathway.
  • It synthesizes findings from genetic, cellular, and clinical studies.

Main Results:

  • The JAK-STAT pathway is fundamental to cellular responses and homeostasis.
  • Dysregulation of this pathway is implicated in various diseases, including primary immunodeficiencies, autoimmune disorders, and cancers.

Conclusions:

  • Understanding the JAK-STAT pathway has revealed its role in numerous diseases.
  • This knowledge has directly led to the development of a new class of therapeutics, JAK inhibitors (Jakinibs).