Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct;18(10):1560-9.
doi: 10.1038/nm.2928. Epub 2012 Sep 16.

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Kazuaki Yoshioka  1 , Kotaro Yoshida, Hong Cui, Tomohiko Wakayama, Noriko Takuwa, Yasuo Okamoto, Wa Du, Xun Qi, Ken Asanuma, Kazushi Sugihara, Sho Aki, Hidekazu Miyazawa, Kuntal Biswas, Chisa Nagakura, Masaya Ueno, Shoichi Iseki, Robert J Schwartz, Hiroshi Okamoto, Takehiko Sasaki, Osamu Matsui, Masahide Asano, Ralf H Adams, Nobuyuki Takakura, Yoh Takuwa
Affiliations

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Kazuaki Yoshioka et al. Nat Med. 2012 Oct.

Abstract

The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles; however, its functional role is not well understood. Global or endothelial-cell-specific deficiency of PI3K-C2α resulted in embryonic lethality caused by defects in sprouting angiogenesis and vascular maturation. PI3K-C2α knockdown in endothelial cells resulted in a decrease in the number of PI3-phosphate-enriched endosomes, impaired endosomal trafficking, defective delivery of VE-cadherin to endothelial cell junctions and defective junction assembly. PI3K-C2α knockdown also impaired endothelial cell signaling, including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. Together, the effects of PI3K-C2α knockdown led to defective endothelial cell migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2α deficiency in vivo suppressed postischemic and tumor angiogenesis and diminished vascular barrier function with a greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2α has a crucial role in vascular formation and barrier integrity and represents a new therapeutic target for vascular disease.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Biol Chem. 2007 Sep 21;282(38):28226-36 - PubMed
    1. Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68 - PubMed
    1. Dev Cell. 2006 Jun;10(6):839-50 - PubMed
    1. Nat Med. 2005 Dec;11(12):1330-8 - PubMed
    1. J Cell Biol. 2007 Jul 30;178(3):517-27 - PubMed

Publication types

MeSH terms

LinkOut - more resources