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A role for Fyn in Trk receptor transactivation by G-protein-coupled receptor signaling

Rithwick Rajagopal1, Moses V Chao

  • 1Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Physiology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.

Molecular and Cellular Neurosciences
|July 25, 2006
PubMed

Insights

G-protein-coupled receptors (GPCRs) can activate Trk receptors without neurotrophins, involving the Src family kinase Fyn. Fyn mediates this transactivation on intracellular membranes, highlighting a novel signaling pathway.

Area of Science:

  • Molecular and Cellular Biology
  • Neuroscience
  • Signal Transduction

Background:

  • Trk receptor tyrosine kinases can be activated independently of neurotrophins via G-protein-coupled receptors (GPCRs).
  • Previous studies suggested GPCR-mediated Trk activation occurs on intracellular membranes, involving second messengers like Src family kinases and calcium.

Purpose of the Study:

  • To elucidate the novel role of the Src family kinase, Fyn, in the signaling pathway between GPCRs and Trk receptors.
  • To investigate the mechanism of GPCR-mediated Trk transactivation.

Main Methods:

  • Investigated Fyn's role in Trk transactivation by adenosine.
  • Examined colocalization of Fyn and Trk using microscopy.
  • Performed in vitro phosphorylation assays to assess Fyn's effect on Trk.

Main Results:

  • Fyn expression enabled Trk transactivation by adenosine.
  • Fyn and Trk were found to be colocalized in a juxtanuclear membrane compartment.
  • Adenosine stimulation activated Fyn, leading to delayed, direct phosphorylation of Trk in vitro.

Conclusions:

  • Fyn acts as a key mediator in GPCR-stimulated Trk transactivation.
  • Fyn is activated by GPCR stimulation and phosphorylates Trk on intracellular membranes.
  • This study reveals a novel mechanism for Trk receptor regulation.

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