Related Experiment Video

Updated: Jul 16, 2026

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
07:12

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

Published on: September 9, 2021

The JAK-STAT signaling pathway: input and output integration

Peter J Murray1

  • 1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38104, USA. peter.murray@stjude.org

Journal of Immunology (Baltimore, Md. : 1950)
|February 22, 2007
PubMed

Insights

The JAK-STAT pathway is crucial for cytokine receptor signaling. New data reveals how suppressor of cytokine signaling (SOCS) proteins diversify this pathway by modulating signal output and gene activation.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • The Janus kinase-STAT (JAK-STAT) pathway is a fundamental signal transduction cascade essential for cytokine receptor signaling.
  • While well-understood, significant gaps exist in knowledge regarding the precise activation and regulation mechanisms of these cascades.
  • The pathway involves interactions between four JAK and seven STAT family members, utilized by nearly 40 cytokine receptors.

Purpose of the Study:

  • To elucidate how regulatory events influence the JAK1-STAT3 pathway, common to IL-6 and IL-10 receptors, leading to diverse gene expression outcomes.
  • To examine receptor preferences for distinct STAT proteins.
  • To address interpretive challenges associated with using STAT-deficient cells and mice in research.

Main Methods:

  • Comparative analysis of IL-6 and IL-10 receptor signaling pathways.
  • Investigation of STAT protein interactions and preferences.
  • Evaluation of suppressor of cytokine signaling (SOCS) protein functions.

Main Results:

  • Diverse gene expression outcomes arise from regulatory events affecting the shared JAK1-STAT3 pathway.
  • Receptor-specific STAT preferences and limitations of STAT-deficient models were considered.
  • Suppressor of cytokine signaling (SOCS) proteins were identified as key regulators of signal quality and quantity.

Conclusions:

  • Regulatory events critically shape JAK-STAT pathway outcomes, leading to varied gene expression.
  • SOCS proteins introduce significant diversity into the JAK-STAT pathway by fine-tuning STAT signal output.
  • Understanding these regulatory mechanisms is vital for comprehending cytokine receptor signaling and its impact on cellular responses.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

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...
Interactions Between Signaling Pathways01:19

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 Cascade01:22

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...
MAPK Signaling Cascades01:07

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...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Intracellular Signaling Cascades01:24

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...