Endothelial-cell-stimulating angiogenesis factor (ESAF) activates progelatinase A (72 kDa type IV collagenase), prostromelysin 1 and procollagenase and reactivates their complexes with tissue inhibitors of metalloproteinases: a role for ESAF in non-inflammatory angiogenesis.
Endothelial-cell-stimulating angiogenesis factor (ESAF) has been shown to activate procollagenase and reactivate complexes of collagenase and gelatinase A with tissue inhibitor of metallo-proteinase (TIMP)-1. In the present paper we show a purification protocol for bovine pineal ESAF and that purified ESAF activates progelatinase A and prostromelysin-1. Unlike the activation of procollagenase by plasmin/plasminogen activator, which requires the presence of stromelysin for full activation, ESAF is able to activate fully all three proenzymes. Purified ESAF is also shown to reactivate the complexes of gelatinase A, collagenase and stromelysin-1 with TIMP-2. Once separated, both enzyme and inhibitor are active; however, ESAF binds to the enzyme in a manner preventing it from further inhibition by TIMP. ESAF is the only physiological molecule able to reactivate the TIMP/enzyme complex.
McLaughlin
B
B
Wolfson Angiogenesis Unit, University of Manchester, Hope Hospital, UK.
Weiss
J B
JB
D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D000818:Animals; D002417:Cattle; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D043925:Angiogenesis Inducing Agents; D004792:Enzyme Precursors; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C022440:procollagenase; C069860:progelatinase; C048047:prostromelysin