The insulin-like growth factor II/mannose 6-phosphate receptor is required for proliferin-induced angiogenesis.
Proliferin stimulates endothelial cell migration in culture and neovascularization in vivo. Previous studies have demonstrated that proliferin can bind to the insulin-like growth factor II/mannose 6-phosphate receptor, and that binding can be blocked by mannose 6-phosphate. We have now found that this receptor plays an essential role in proliferin-induced angiogenesis. Proliferin binding to endothelial cells is blocked by the addition of mannose 6-phosphate, as is the ability of both recombinant and placental-derived proliferin to stimulate the migration of capillary endothelial cells in vitro and to induce neovascularization in the rat cornea. Consistent with a direct role of this receptor in angiogenesis, insulin-like growth factor II, as well as a mutant form of insulin-like growth factor II that binds to the insulin-like growth factor II/mannose 6-phosphate receptor but not to the insulin-like growth factor I receptor, also stimulate endothelial cell migration and neovascularization.
Volpert
O
O
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Jackson
D
D
Bouck
N
N
Linzer
D I
DI
D000818:Animals; D002417:Cattle; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008360:Mannosephosphates / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000502:physiology*; D011994:Recombinant Proteins
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008360:Mannosephosphates; C000634106:Prl2c2 protein, mouse; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II; D011388:Prolactin