The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors.
Serine proteases are involved in many processes in the nervous system and specific inhibitors tightly control their proteolytic activity. Thrombin is thought to play a role in tissue development and homeostasis. To date, protease nexin-1 is the only known endogenous protease inhibitor that specifically interferes with thrombotic activity and is expressed in the brain. In this study, we report the detection of a novel thrombin inhibitory activity in the brain of protease nexin-1(-/-) mice. Purification and subsequent analysis by tandem mass spectrometry identified this protein as the phosphatidylethanolamine-binding protein (PEBP). We demonstrate that PEBP exerts inhibitory activity against several serine proteases including thrombin, neuropsin, and chymotrypsin, whereas trypsin, tissue type plasminogen activator, and elastase are not affected. Since PEBP does not share significant homology with other serine protease inhibitors, our results define it as the prototype of a novel class of serine protease inhibitors. PEBP immunoreactivity is found on the surface of Rat-1 fibroblast cells and although its sequence contains no secretion signal, PEBP-H(6) can be purified from the conditioned medium upon recombinant expression.
Hengst
U
U
Friedrich Miescher Institute, Maulbeerstrasse 66, CH 4058 Basel, Switzerland.
Albrecht
H
H
Hess
D
D
Monard
D
D
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor; D000727:Androgen-Binding Protein; D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism; D007610:Kallikreins; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D011233:Precipitin Tests; D060789:Prostatein; D058255:Protease Nexins; D051381:Rats; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D060765:Secretoglobins; D020539:Sequence Analysis, Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D058258:Serpin E2; D021241:Spectrometry, Mass, Electrospray Ionization; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014598:Uteroglobin; D060788:Mammaglobin B
D016564:Amyloid beta-Protein Precursor; D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D002918:Chymotrypsin; D007610:Kallikreins; D008565:Membrane Proteins; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D060789:Prostatein; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D060765:Secretoglobins; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D058258:Serpin E2; D013917:Thrombin; D014598:Uteroglobin; C511482:PEBP1 protein, human; C545486:SERPINE2 protein, human; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C094799:KLK8 protein, human; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B