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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...

Cell-surface Signaling

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.

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...

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...

Cell Signaling Feedback Loops

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...

Autocrine Signaling

Autocrine Signaling

Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...

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Related Experiment Video

Updated: Jun 5, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Cytokine signaling exposed.

Stevan R Hubbard¹

¹Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. stevan.hubbard@med.nyu.edu

Structure (London, England : 1993)

|January 12, 2011

Summary

This summary is machine-generated.

Researchers visualized a complete cytokine signaling complex, revealing how cytokine-receptor binding activates Janus kinases (JAKs) through trans-phosphorylation. This provides crucial insights into cellular communication and immune response regulation.

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Area of Science:

Cellular Biology
Molecular Biology
Immunology

Background:

Cytokine signaling is crucial for immune responses and cellular communication.
The precise mechanism of Janus kinase (JAK) activation following cytokine receptor binding remained incompletely understood.

Discussion:

Lupardus et al. present electron microscopy images of a complete cytokine signaling complex.
These images offer structural insights into the initial steps of cytokine signal transduction.
The findings illuminate the process of receptor-mediated Janus kinase (JAK) activation.

Key Insights:

Visualized the complete cytokine signaling complex using electron microscopy.
Provided mechanistic clues for how cytokine binding initiates JAK trans-phosphorylation.
Enhanced understanding of the molecular events triggering cellular responses to cytokines.

Outlook:

Further structural studies can elucidate the dynamics of the signaling complex.
This work may inform the development of targeted therapies for immune-related diseases.
Understanding JAK activation is key for modulating immune cell function.