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PMID:2457905

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Citation

Bicknell, R and Vallee, BL (1988) Angiogenin activates endothelial cell phospholipase C. Proc. Natl. Acad. Sci. U.S.A. 85:5961-5

Abstract

Low concentrations of angiogenin activate the inositol-specific phospholipase C of cultured pulmonary artery, umbilical vein, and capillary endothelial cells, promoting a transient increase in the intracellular levels of 1,2-diacylglycerol and inositol trisphosphate. The response is strongly dose dependent with a maximum in the ng/ml concentration range and, for some cell lines, a marked decrease at concentrations greater than 1 ng/ml; e.g., arterial endothelial cells respond weakly to angiogenin concentrations comparable to that in normal human plasma (approximately equal to 400 ng/ml). Chemical modification of the active site of angiogenin or inhibition with placental ribonuclease inhibitor abolishes its activation of endothelial cell phospholipase C; this correlates with the concomitant loss of both intrinsic ribonucleolytic and angiogenic activity. The response to low concentrations of angiogenin is consistent with its potency of inducing vascularization in classical angiogenesis assays. In vivo, endothelial cells are exposed to concentrations of angiogenin higher than that required to elicit a cellular response; it seems likely, therefore, that expression of a surface receptor or some other process must be rate limiting in the cellular response.

Links

PubMed PMC281885

Keywords

Animals; Cattle; Cells, Cultured; Diglycerides/biosynthesis; Dose-Response Relationship, Drug; Endothelium, Vascular/drug effects; Endothelium, Vascular/enzymology; Enzyme Activation/drug effects; Humans; Neoplasm Proteins/pharmacology; Neovascularization, Pathologic; Phorbol Esters/pharmacology; Phosphatidylinositols/metabolism; Protein Kinases/analysis; Ribonuclease, Pancreatic; Ribonucleases/pharmacology; Structure-Activity Relationship; Type C Phospholipases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ANGI

enables

GO:0019843: rRNA binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ANGI

involved_in

GO:0006651: diacylglycerol biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ANGI

involved_in

GO:0007202: activation of phospholipase C activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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