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- Title
Parathyroid hormone?related peptide is a naturally occurring, protein kinase A?dependent angiogenesis inhibitor.
- Authors
Bakre, Manjiri M.; Zhu, Yuhong; Yin, Hong; Burton, Doug W.; Terkeltaub, Robert; Deftos, Leonard J.; Varner, Judith A.
- Abstract
Angiogenesis is a highly regulated process that results from the sequential actions of naturally occurring stimulators and inhibitors. Here, we show that parathyroid hormone?related peptide, a peptide hormone derived from normal and tumor cells that regulates bone metabolism and vascular tone, is a naturally occurring angiogenesis inhibitor. Parathyroid hormone?related peptide or a ten-amino-acid peptide from its N terminus inhibits endothelial cell migration in vitro and angiogenesis in vivo by activating endothelial cell protein kinase A. Activation of protein kinase A inhibits cell migration and angiogenesis by inhibiting the small GTPase Rac. In contrast, inhibition of protein kinase A reverses the anti-migratory and anti-angiogenic properties of parathyroid hormone?related peptide. These studies show that parathyroid hormone?related peptide is a naturally occurring angiogenesis inhibitor that functions by activation of protein kinase A.
- Subjects
PARATHYROID hormone-related protein; PEPTIDE hormones; PROTEIN kinases; NEOVASCULARIZATION
- Publication
Nature Medicine, 2002, Vol 8, Issue 9, p995
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm753