Yan W, Wu F, Morser J, Wu Q
Department of Cardiovascular Research, Berlex Biosciences, 15049 San Pablo Avenue, Richmond, CA 94804, USA.
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8525-9. doi: 10.1073/pnas.150149097.
Atrial natriuretic peptide (ANP) is a cardiac hormone essential for the regulation of blood pressure. In cardiac myocytes, ANP is synthesized as a precursor, pro-ANP, that is converted to biologically active ANP by an unknown membrane-associated protease. Recently, we cloned a transmembrane serine protease, corin, that is highly expressed in the heart. In this study, we examine effects of corin on pro-ANP processing. Our results show that recombinant human corin converts pro-ANP to ANP and that the cleavage in pro-ANP by corin is highly sequence specific. Our findings suggest that corin is the long-sought pro-ANP-converting enzyme and that the corin-mediated pro-ANP activation may play a role in regulating blood pressure.
心房利钠肽(ANP)是一种对血压调节至关重要的心脏激素。在心肌细胞中,ANP以一种前体形式即前ANP合成,该前体由一种未知的膜相关蛋白酶转化为具有生物活性的ANP。最近,我们克隆了一种跨膜丝氨酸蛋白酶——corin,它在心脏中高度表达。在本研究中,我们检测了corin对前ANP加工的影响。我们的结果表明,重组人corin可将前ANP转化为ANP,并且corin对前ANP的切割具有高度的序列特异性。我们的发现提示,corin就是长期以来寻找的前ANP转化酶,并且corin介导的前ANP激活可能在血压调节中发挥作用。