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Pharmacol Res. 2017 Jan;115:107-123. doi: 10.1016/j.phrs.2016.11.022. Epub 2016 Nov 23.

Modulation of VEGF receptor 2 signaling by protein phosphatases.

Author information

1
Yale Cardiovascular Research Center, Department of Internal Medicine and Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: federico.corti@yale.edu.
2
Yale Cardiovascular Research Center, Department of Internal Medicine and Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: michael.simons@yale.edu.

Abstract

Phosphorylation of serines, threonines, and tyrosines is a central event in signal transduction cascades in eukaryotic cells. The phosphorylation state of any particular protein reflects a balance of activity between kinases and phosphatases. Kinase biology has been exhaustively studied and is reasonably well understood, however, much less is known about phosphatases. A large body of evidence now shows that protein phosphatases do not behave as indiscriminate signal terminators, but can function both as negative or positive regulators of specific signaling pathways. Genetic models have also shown that different protein phosphatases play precise biological roles in health and disease. Finally, genome sequencing has unveiled the existence of many protein phosphatases and associated regulatory subunits comparable in number to kinases. A wide variety of roles for protein phosphatase roles have been recently described in the context of cancer, diabetes, hereditary disorders and other diseases. In particular, there have been several recent advances in our understanding of phosphatases involved in regulation of vascular endothelial growth factor receptor 2 (VEGFR2) signaling. The receptor is the principal signaling molecule mediating a wide spectrum of VEGF signal and, thus, is of paramount significance in a wide variety of diseases ranging from cancer to cardiovascular to ophthalmic. This review focuses on the current knowledge about protein phosphatases' regulation of VEGFR2 signaling and how these enzymes can modulate its biological effects.

KEYWORDS:

Angiogenesis; Blood vessels; Endothelial cells; Protein phosphatases; VEGFR2 signaling

PMID:
27888154
PMCID:
PMC5205541
DOI:
10.1016/j.phrs.2016.11.022
[Indexed for MEDLINE]
Free PMC Article

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