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Updated: May 1, 2026

Oligomerization Dynamics of Cell Surface Receptors in Living Cells by Total Internal Reflection Fluorescence Microscopy Combined with Number and Brightness Analysis
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Cellular responses to FGF1 are modulated by palmitoylation of the docking protein FRS2α

Seong J An1, Yoshihisa Suzuki1, Jyotidarsini Mohanty1

  • 1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520.

Proceedings of the National Academy of Sciences of the United States of America
|April 29, 2026
PubMed

Insights

Palmitoylation of the FRS2α docking protein stabilizes its membrane association, enhancing fibroblast growth factor (FGF)-induced signaling. Full FGF signaling and neuronal differentiation require dual palmitoylation sites on FRS2α.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Biochemistry

Background:

  • Receptor tyrosine kinases (RTKs) mediate cellular responses via signaling complexes.
  • Docking proteins like FRS2α act as crucial signaling hubs for growth factors.
  • FRS2α is activated by fibroblast growth factors (FGFs) and other extracellular signals.

Purpose of the Study:

  • To investigate the role of FRS2α palmitoylation in membrane association and signaling.
  • To determine the impact of specific palmitoylation sites on FGF-induced cellular responses.
  • To elucidate the necessity of FRS2α palmitoylation for FGF-mediated neuronal differentiation.

Main Methods:

  • Site-directed mutagenesis to create FRS2α palmitoylation-deficient mutants.
  • Analysis of FRS2α membrane association using biochemical assays.
  • Assessment of FGF1-induced signaling pathways, including MAPK activation.
  • Evaluation of cellular processes like cytoskeletal reorganization and neuronal differentiation in PC12 cells.

Main Results:

  • Palmitoylation at two specific sites stabilizes FRS2α's association with the plasma membrane.
  • Partial rescue of FGF1-induced MAPK activation and cellular responses was observed with single palmitoylation site mutants.
  • Full restoration of signaling strength and cellular activities required dual palmitoylation of FRS2α.
  • FGF1-induced neuronal differentiation in PC12 cells was strictly dependent on FRS2α palmitoylation.

Conclusions:

  • Dual palmitoylation of FRS2α is essential for robust membrane anchoring and efficient signaling.
  • FRS2α palmitoylation creates a platform for assembling signaling complexes involved in cytoskeletal dynamics.
  • Palmitoylation of FRS2α is indispensable for FGF-driven neuronal differentiation, highlighting its critical role beyond proliferation.
Keywords:
cell signalingmyristoylationpalmitoylationphosphorylationreceptor tyrosine kinases

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