PUBLICATION
cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner
- Authors
- Nedvetsky, P.I., Zhao, X., Mathivet, T., Aspalter, I.M., Stanchi, F., Metzger, R.J., Mostov, K.E., Gerhardt, H.
- ID
- ZDB-PUB-161007-15
- Date
- 2016
- Source
- Development (Cambridge, England) 143: 3582-3590 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Notch, Retina, Signal transduction, Sprouting, Vascular development
- MeSH Terms
-
- Animals
- Cell Movement/genetics
- Cell Movement/physiology
- Cyclic AMP-Dependent Protein Kinases/genetics
- Cyclic AMP-Dependent Protein Kinases/metabolism*
- Endothelial Cells/cytology*
- Endothelial Cells/metabolism*
- Mice
- Mice, Mutant Strains
- Neovascularization, Physiologic/genetics
- Neovascularization, Physiologic/physiology*
- Polymerase Chain Reaction
- Receptors, Notch/metabolism*
- Retina/cytology*
- Retina/metabolism*
- Signal Transduction/genetics
- Signal Transduction/physiology
- Zebrafish
- PubMed
- 27702786 Full text @ Development
Citation
Nedvetsky, P.I., Zhao, X., Mathivet, T., Aspalter, I.M., Stanchi, F., Metzger, R.J., Mostov, K.E., Gerhardt, H. (2016) cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner. Development (Cambridge, England). 143:3582-3590.
Abstract
cAMP-dependent protein kinase A (PKA) is a ubiquitously expressed serine/threonine kinase that regulates a variety of cellular functions. Here, we demonstrate that endothelial PKA activity is essential for vascular development, specifically regulating the transition from sprouting to stabilization of nascent vessels. Inhibition of endothelial PKA by endothelial cell-specific expression of dominant-negative PKA in mice led to perturbed vascular development, hemorrhage and embryonic lethality at mid-gestation. During perinatal retinal angiogenesis, inhibition of PKA resulted in hypersprouting as a result of increased numbers of tip cells. In zebrafish, cell autonomous PKA inhibition also increased and sustained endothelial cell motility, driving cells to become tip cells. Although these effects of PKA inhibition were highly reminiscent of Notch inhibition effects, our data demonstrate that PKA and Notch independently regulate tip and stalk cell formation and behavior.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping