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Akt is a major angiogenic mediator downstream of the Ang1/Tie2 signaling pathway

Laura M DeBusk1, Dennis E Hallahan, Pengnian Charles Lin

  • 1Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Experimental Cell Research
|July 10, 2004
PubMed

Insights

Akt is essential for angiopoietin-1 (Ang1)-mediated endothelial cell (EC) survival and sprouting. While Akt is crucial for Ang1 signaling, it is only sufficient, not required, for vascular endothelial growth factor (VEGF)-mediated EC survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Angiogenesis Research

Background:

  • Tyrosine kinases Tie2 and VEGF receptors (VEGFRs) are critical for angiogenesis.
  • Both Tie2 and VEGFR activation converge on Akt, a key mediator of endothelial cell (EC) survival and motility.

Purpose of the Study:

  • To compare the distinct roles of Akt in Tie2-mediated versus VEGF-mediated EC survival and sprouting.
  • To elucidate the signaling pathways downstream of Angiopoietin-1 (Ang1) and Vascular Endothelial Growth Factor (VEGF).

Main Methods:

  • Investigated EC survival and sprouting using Ang1 and VEGF signaling pathways.
  • Manipulated Akt activity through blockade and activation to assess its necessity and sufficiency.
  • Utilized a three-dimensional collagen gel model to study EC sprouting.

Main Results:

  • Akt is required and sufficient for Ang1-induced EC survival, with Akt blockade abolishing survival and Akt activation rescuing apoptosis.
  • Akt is sufficient but not required for VEGF-mediated EC survival; Akt activation rescues VEGF blockade-induced apoptosis, but Akt blockade has no effect.
  • Both Ang1 and VEGF induce EC sprouting, which is dependent on Akt activation, with Akt blockade inhibiting sprouting.

Conclusions:

  • Akt is the primary mediator of Ang1-induced EC survival, whereas VEGF utilizes multiple pathways for EC survival.
  • Akt is essential and sufficient for mediating EC sprouting induced by both Ang1 and VEGF.
  • Differential roles of Akt in EC survival highlight distinct signaling mechanisms downstream of Tie2 and VEGFR.

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