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Updated: Jun 19, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Spred2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling

Faraz K Mardakheh1, Mona Yekezare, Laura M Machesky

  • 1Cancer Research UK Growth Factor Group, University of Birmingham, Birmingham B15 2TT, England, UK.

The Journal of Cell Biology
|October 14, 2009
PubMed

Insights

Sprouty related with EVH1 domain (Spred) proteins inhibit fibroblast growth factor (FGF) signaling. Neighbor of BRCA1 (NBR1) protein binding to Spred2 redirects FGF receptors for degradation, down-regulating signaling.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Cancer research

Background:

  • Endocytic trafficking of receptors modulates growth factor signaling.
  • Sprouty related with EVH1 domain (Spred) proteins are inhibitors of signaling pathways.
  • The tumor-suppressive functions of Spreds are proposed but not fully understood.

Purpose of the Study:

  • To investigate the mechanism by which Spred proteins regulate fibroblast growth factor (FGF) signaling.
  • To identify proteins that interact with the EVH1 domain of Spred2.
  • To elucidate the role of Neighbor of BRCA1 (NBR1) in Spred2-mediated inhibition of FGF signaling.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Confocal microscopy to assess protein colocalization.
  • Analysis of FGF signaling pathway activation and receptor trafficking.

Main Results:

  • Identified Neighbor of BRCA1 (NBR1) as a novel late endosomal protein that binds to the EVH1 domain of Spred2.
  • Demonstrated that NBR1 interacts and colocalizes with Spred2 in vivo.
  • Showed that Spred2-mediated attenuation of FGF signaling is dependent on NBR1 and involves lysosomal degradation of activated FGF receptors.

Conclusions:

  • NBR1 plays a critical role in regulating receptor trafficking.
  • Spred2 down-regulates FGF signaling by interacting with NBR1, which redirects activated receptors for lysosomal degradation.
  • This study provides a novel molecular mechanism for Spred2-mediated signaling inhibition.

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