FURIN HAS THE PROALBUMIN SUBSTRATE-SPECIFICITY AND SERPIN INHIBITORY PROPERTIES OF AN IN-SITU HEPATIC CONVERTASE
FURIN HAS THE PROALBUMIN SUBSTRATE-SPECIFICITY AND SERPIN INHIBITORY PROPERTIES OF AN IN-SITU HEPATIC CONVERTASE
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DOI：
10.1016/0014-5793(94)80353-6
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发表时间：
1994-01-31
期刊：
影响因子：
3.5
通讯作者：
NAKAYAMA, K
中科院分区：
文献类型：
--
作者：
BRENNAN, SO;NAKAYAMA, K
Furin是一种在肝脏中具有高RNA表达的KEX2蛋白酶同源物，是肝脏蛋白转化酶的理想候选物。本研究表明纯化的重组呋喃具有与原位肝转化酶相同的原白蛋白特异性和丝氨酸抑制特性。正常人原白蛋白- rrd -位点有快速的裂解，而天然未加工的- rrv -、- hrd -、- rqd -或- crd -裂解位点序列的变体没有明显的裂解。s -氨基乙基化不增加后者的裂解。Furin被α(1)-抗胰蛋白酶Pittsburgh （358 Met- >Arg）特异性抑制（K1/2 = 3 μ M），但不被50 μ M正常的抗胰蛋白酶M或抗凝血酶抑制，然而，抗凝血酶/肝素是一个很好的抑制剂（K1/2 = 9 μ M）。白蛋白原裂解的最佳pH值在5.5 ~ 6.0之间，这表明furin在分泌囊泡（白蛋白原裂解的部位）内具有充分活性。
Furin, a KEX2 protease homolog with high RNA expression in the liver is an excellent candidate as a hepatic proprotein convertase. Here we show that purified recombinant furin has the same proalbumin specificity and serpin inhibitory properties as the in situ hepatic convertase. There was rapid cleavage at the -RRD- site of normal human proalbumin but there no significant cleavage of natural unprocessed Variants with cleavage site sequences of -RRV-, -HRD-, -RQD-, or -CRD-. Cleavage of the latter was not increased by S-aminoethylation. Furin was specifically inhibited by alpha(1)-antitrypsin Pittsburgh (358 Met-->Arg), (K1/2 = 3 mu M) but not by 50 mu M normal antitrypsin M or by antithrombin, however, antithrombin/heparin was a good inhibitor (K1/2 = 9 mu M). The pH optimum for proalbumin cleavage was between pH 5.5 and 6.0, indicating that furin is potentially fully active within secretory vesicles, the site of proalbumin cleavage.