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cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner

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Item Type:Article
Title:cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner
Creators Name:Nedvetsky, P.I. and Zhao, X. and Mathivet, T. and Aspalter, I.M. and Stanchi, F. and Metzger, R.J. and Mostov, K.E. and Gerhardt, H.
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.
Keywords:Notch, Angiogenesis, Retina, Signal Transduction, Sprouting, Vascular Development, Animals, Mice, Zebrafish
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists
Volume:143
Number:19
Page Range:3582-3590
Date:4 October 2016
Official Publication:https://doi.org/10.1242/dev.134767
PubMed:View item in PubMed

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