Ribonuclease inhibitor regulates neovascularization by human angiogenin.
Human angiogenin (ANG) is a homologue of bovine pancreatic ribonuclease (RNase A) that induces neovascularization. ANG is the only human angiogenic factor that possesses ribonucleolytic activity. To stimulate blood vessel growth, ANG must be transported to the nucleus and must retain its catalytic activity. Like other mammalian homologues of RNase A, ANG forms a femtomolar complex with the cytosolic ribonuclease inhibitor protein (RI). To determine whether RI affects ANG-induced angiogenesis, we created G85R/G86R ANG, which possesses 10(6)-fold lower affinity for RI but retains wild-type ribonucleolytic activity. The neovascularization of rabbit corneas by G85R/G86R ANG was more pronounced and more rapid than by wild-type ANG. These findings provide the first direct evidence that RI serves to regulate the biological activity of ANG in vivo.
Dickson
Kimberly A
KA
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706-1544, USA.
Kang
Dong-Ku
DK
Kwon
Young Sam
YS
Kim
Jae Chan
JC
Leland
Peter A
PA
Kim
Byung-Moon
BM
Chang
Soo-Ik
SI
Raines
Ronald T
RT
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000502:physiology*; D012260:Ribonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004791:Enzyme Inhibitors; D012260:Ribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic