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Internalization of fibroblast growth factor receptor is inhibited by a point mutation at tyrosine 766

A Sorokin1, M Mohammadi, J Huang

  • 1Department of Pharmacology, New York University Medical Center, New York 10016.

The Journal of Biological Chemistry
|June 24, 1994
PubMed

Insights

Fibroblast growth factor receptor (FGFR) phosphorylation at Tyr-766 is crucial for its internalization and degradation. Mutating this site impairs receptor trafficking, affecting cellular response to FGF signaling.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Fibroblast growth factor (FGF) binding to its receptor (FGFR) triggers receptor autophosphorylation.
  • Specific tyrosine residues on the FGFR are critical for downstream signaling pathways.

Purpose of the Study:

  • To investigate the role of tyrosine residue 766 (Tyr-766) phosphorylation in FGF receptor trafficking.
  • To determine if Tyr-766 is essential for receptor internalization, down-regulation, and degradation.

Main Methods:

  • Expression of wild-type FGF receptor 1 (flg) and a Y766F mutant receptor in rat myoblasts and Ba/F3 cells.
  • Analysis of FGF receptor internalization, down-regulation, and degradation following ligand binding.
  • Comparison of cellular trafficking between wild-type and mutant receptors.

Main Results:

  • The Y766F mutation significantly decreased FGF receptor internalization.
  • Ligand-induced FGF receptor down-regulation and degradation were reduced in the Y766F mutant.
  • Phosphorylation of Tyr-766 is essential for FGF receptor cellular trafficking.

Conclusions:

  • Tyrosine 766 phosphorylation is a key regulatory event for FGF receptor trafficking.
  • The Y766F mutation disrupts normal receptor cellular dynamics, impacting FGF signaling.
  • This finding highlights the multifaceted role of Tyr-766 beyond phospholipase C gamma interaction.

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