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Sprouty: how does the branch manager work?

Graeme R Guy1, Esther S M Wong, Permeen Yusoff

  • 1Signal Transduction Laboratory, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117 609, Republic of Singapore. mcbgg@imcb.nus.edu.sg

Journal of Cell Science
|June 28, 2003
PubMed
Summary
This summary is machine-generated.

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Sprouty (Spry) proteins modulate the Ras/MAP-kinase pathway. Spry2

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Protein interactions

Background:

  • Sprouty (Spry) proteins are novel modulators of the Ras/MAP-kinase signaling pathway.
  • Conserved sequences in Spry proteins suggest roles in protein-protein interactions and localization to the plasma membrane.
  • Spry proteins influence signaling downstream of receptor tyrosine kinases (RTKs).

Purpose of the Study:

  • To elucidate the mechanism of action of Sprouty (Spry) proteins, particularly Spry2, in regulating the Ras/MAP-kinase pathway.
  • To investigate the differential effects of Spry2 on MAP kinase activation downstream of epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR).

Main Methods:

  • Studies were conducted using cultured mammalian cells.
  • Investigated protein interactions between Spry2 and Cbl.

Related Experiment Videos

  • Examined the effects of Spry2 on receptor endocytosis and MAP kinase activation.

    • Main Results:

    • Human Spry2 (hSpry2) inhibits epidermal growth factor receptor (EGFR) endocytosis, sustaining MAP kinase activation.
    • hSpry2 negatively regulates MAP kinase activation downstream of fibroblast growth factor receptors (FGFRs).
    • Cbl protein directly interacts with Spry2 upon receptor tyrosine kinase (RTK) activation.

    Conclusions:

    • Spry2 exhibits differential regulation of the Ras/MAP-kinase pathway depending on the activated receptor tyrosine kinase (RTK).
    • The E3 ubiquitin ligase and docking protein functions of Cbl are critical for mediating Spry2's distinct effects on signaling.
    • Understanding Spry protein function provides insights into cellular signaling regulation.