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Updated: Jun 5, 2026

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

Sprouty proteins: antagonists of endothelial cell signaling and more

Miguel A Cabrita1, Gerhard Christofori

  • 1Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, University of Basel, Basel, Switzerland.

Thrombosis and Haemostasis
|September 30, 2003
PubMed

Insights

Sprouty proteins (Sprys) are key regulators of receptor tyrosine kinase (RTK) signaling. These proteins can inhibit or enhance mitogen-activated protein kinase (MAPK) pathway activation, adding complexity to cellular responses to growth factors.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Signal transduction

Background:

  • Receptor tyrosine kinases (RTKs) activate the mitogen-activated protein kinase (MAPK) pathway, influencing cell proliferation, differentiation, and motility.
  • The precise regulation of RTK signaling and differential cellular responses to growth factors remain incompletely understood.
  • Sprouty (Spry) proteins, discovered in Drosophila, act as inhibitors of RTK-induced MAPK activation, offering insights into signal regulation.

Purpose of the Study:

  • To review the functional characteristics of mammalian Spry proteins (Spry1-4).
  • To explore the dual roles of Sprys in regulating growth factor-induced MAPK activation.
  • To elucidate the molecular mechanisms underlying Spry function and their interactions with signaling partners.

Main Methods:

  • Review of existing literature on Spry proteins and their roles in RTK signaling.
  • Analysis of Spry interactions with MAPK pathway components and other binding partners.
  • Discussion of the role of tyrosine phosphorylation in Spry function.

Main Results:

  • Mammalian Sprys function as ligand-induced feedback inhibitors of growth factor receptors.
  • Sprys exhibit context-dependent roles: inhibiting MAPK in endothelial cells (FGF/VEGF signaling) but enhancing it in EGF-stimulated cells.
  • Sprys interact with multiple MAPK pathway effectors, and their function requires tyrosine phosphorylation.

Conclusions:

  • Sprys represent a complex regulatory layer in RTK-mediated signal transduction.
  • The dual function of Sprys, dependent on binding partners and phosphorylation, helps explain variations in cellular responses to growth factors.
  • Further research into Spry interactions can elucidate the intricacies of growth factor signaling pathways.

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