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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...

cAMP-dependent Protein Kinase Pathways

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

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...

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 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...

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...

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Related Experiment Video

Updated: May 25, 2026

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Published on: August 10, 2014

The Jak/STAT pathway is involved in synaptic plasticity.

Céline S Nicolas¹, Stéphane Peineau, Mascia Amici

¹MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.

|January 31, 2012

Summary

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for brain synaptic plasticity. This pathway regulates NMDA-receptor dependent long-term depression in the hippocampus.

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Last Updated: May 25, 2026

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

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3D Modeling of Dendritic Spines with Synaptic Plasticity

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Area of Science:

Neuroscience
Molecular Biology
Cell Signaling

Background:

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway regulates critical cellular processes like cell growth, differentiation, immune functions, and cancer.
JAK2 and STAT3 are highly expressed in the brain, particularly in the postsynaptic density (PSD).

Purpose of the Study:

To investigate a novel neuronal function of the JAK/STAT pathway.
To determine the role of the JAK/STAT pathway in synaptic plasticity, specifically in NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus.

Main Methods:

Utilized a variety of complementary experimental approaches.
Focused on the hippocampus to study NMDAR-LTD induction.

Main Results:

Demonstrated that the JAK/STAT pathway plays an essential role in the induction of NMDAR-LTD.
Confirmed the presence and function of JAK2 and STAT3 in the PSD.

Conclusions:

The JAK/STAT pathway has a significant role in synaptic plasticity within the brain.
Beyond its established roles in cytokine signaling, the JAK/STAT pathway is implicated in neuronal function and learning/memory processes.