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Emerging roles of post-translational modifications in signal transduction and angiogenesis

Nader Rahimi1, Catherine E Costello

  • 1Department of Pathology, Boston University School of Medicine, Boston, MA, USA.

Proteomics
|August 28, 2014
PubMed

Insights

Vascular endothelial growth factor receptor-2 (VEGFR-2) post-translational modifications (PTMs) are crucial for angiogenesis. Understanding these VEGFR-2 PTMs reveals their role in signaling and potential therapeutic applications.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase vital for blood vessel formation (vasculogenesis) and abnormal blood vessel growth (pathological angiogenesis).
  • Post-translational modifications (PTMs) of VEGFR-2 are increasingly recognized for their critical roles in regulating endothelial cell functions essential for angiogenesis, including differentiation, proliferation, migration, and permeability.

Purpose of the Study:

  • To review the diverse post-translational modifications (PTMs) identified on VEGFR-2.
  • To elucidate the functional significance of these VEGFR-2 PTMs in angiogenic signaling pathways.
  • To explore the potential of targeting VEGFR-2 PTMs for novel therapeutic strategies.

Main Methods:

  • Review of recent mass spectrometry (MS) analyses identifying novel PTMs on VEGFR-2.
  • Analysis of the structural localization of PTMs on both extracellular (N-glycosylation) and cytoplasmic domains (phosphorylation, methylation, acetylation, ubiquitination) of VEGFR-2.
  • Synthesis of current literature on the functional impact of VEGFR-2 PTMs.

Main Results:

  • VEGFR-2 possesses multiple PTMs, including N-glycosylation on its extracellular domains and Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation, and ubiquitination on its cytoplasmic domain.
  • These PTMs create a dynamic signaling system that precisely controls angiogenic responses.
  • Newly identified PTMs on VEGFR-2 exhibit distinct functional roles in regulating angiogenic signaling.

Conclusions:

  • Post-translational modifications significantly diversify VEGFR-2 signaling, enabling complex regulation of angiogenesis.
  • A comprehensive understanding of VEGFR-2 PTMs is essential for deciphering angiogenic processes.
  • Targeting VEGFR-2 PTMs presents promising avenues for developing innovative therapies for angiogenesis-related diseases.
Keywords:
AcetylationCell biologyGlycosylationPhosphorylationTandem mass spectrometryVEGF receptor

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