Related Experiment Video

Updated: Aug 19, 2026

Whole-mount Imaging of Mouse Embryo Sensory Axon Projections
08:37

Whole-mount Imaging of Mouse Embryo Sensory Axon Projections

Published on: December 9, 2014

Activation of STAT5-dependent transcription by the neurotrophin receptor Trk

Mathias Klein1, Barbara L Hempstead, Kenneth K Teng

  • 1Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.

Journal of Neurobiology
|February 11, 2005
PubMed

Insights

Neurotrophins activate the transcription factor STAT5 through Trk receptors, influencing gene expression. This process bypasses JAK2, relying instead on Src kinase, offering new insights into neuronal signaling pathways.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Neurotrophins, such as nerve growth factor (NGF), are crucial for neuronal development and survival.
  • Their biological effects are mediated by Trk receptor tyrosine kinases, involving complex cellular events.
  • Signal transduction pathways downstream of Trk receptors are not fully elucidated.

Purpose of the Study:

  • To investigate a novel signaling pathway linking activated Trk receptors to the transcription factor STAT5.
  • To determine the role of specific Trk receptor domains and upstream kinases in STAT5 activation.
  • To explore the implications for neurotrophin-regulated gene expression in neurons.

Main Methods:

  • Luciferase reporter assays using a STAT5-responsive promoter element.
  • Structure-function analysis of Trk A receptor mutants in heterologous cells.
  • Reconstitution studies in JAK2-deficient cell lines and inhibition studies with Src kinase inhibitors.

Main Results:

  • Neurotrophin activation of Trk A, B, and C receptors induces STAT5-mediated transcription.
  • Trk A kinase activity and an intact phospholipase C-gamma binding site are essential for STAT5 activation.
  • Neurotrophin-induced STAT5 activation is JAK2-independent but sensitive to Src kinase inhibition.

Conclusions:

  • Neurotrophins activate STAT5 via a novel signaling cascade involving Trk receptors.
  • This pathway regulates neuronal gene expression independently of JAK2, highlighting the role of Src kinase.
  • Findings provide new molecular insights into neurotrophin signaling in the nervous system.

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

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells07:12

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

Published on: September 9, 2021

Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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...
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...