IDENTIFICATION OF A CDNA-ENCODING A 2ND PUTATIVE PROHORMONE CONVERTASE RELATED TO PC2 IN ATT20 CELLS AND ISLETS OF LANGERHANS
IDENTIFICATION OF A CDNA-ENCODING A 2ND PUTATIVE PROHORMONE CONVERTASE RELATED TO PC2 IN ATT20 CELLS AND ISLETS OF LANGERHANS
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DOI：
10.1073/pnas.88.2.340
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发表时间：
1991-01-01
影响因子：
11.1
通讯作者：
STEINER, DF
中科院分区：
文献类型：
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作者：
SMEEKENS, SP;AVRUCH, AS;STEINER, DF
PC 2和弗林蛋白酶是两个最近鉴定的成员一类哺乳动物蛋白同源的酵母前体加工蛋白酶kex 2和细菌枯草杆菌蛋白酶。 我们已经使用的聚合酶链反应，以确定和克隆的cDNA（PC 3）从小鼠AtT 20垂体前叶细胞系，代表这个不断增长的哺乳动物蛋白酶家族的一个额外的成员。 PC 3编码一个753个残基的蛋白质，该蛋白质以信号肽开始，并且含有与PC 2、弗林蛋白酶和kex 2的催化模块密切相关的292个残基的结构域。 在该区域内，PC 3的58%、65%和50%的氨基酸分别与比对的PC 2、弗林蛋白酶和kex 2序列相同，并且催化重要的Asp、His和Ser残基都是保守的。 在北方印迹上，PC 3与3和5种酶的两种转录物杂交。 组织分布研究表明，PC 2和PC 3在多种神经内分泌组织中表达，包括胰岛和脑，但在肝脏、肾脏、骨骼肌和脾脏中不表达。 PC 3、PC 2和弗林蛋白酶的高度相似性表明它们都是参与激素原和/或其他蛋白质前体加工的哺乳动物蛋白酶超家族的成员。 与弗林蛋白酶相比，PC 3与PC 2一样，缺乏疏水性跨膜锚，但它具有类似于羧肽酶H的假定膜锚的潜在C-末端两亲性螺旋片段。 这些和其他差异表明，这些蛋白质在细胞内进行区室化的蛋白水解，如在调节与组成性分泌途径内的加工。
PC2 and furin are two recently identified members of a class of mammalian proteins homologous to the yeast precursor processing protease kex2 and the bacterial subtilisins. We have used the polymerase chain reaction to identify and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that represents an additional member of this growing family of mammalian proteases. PC3 encodes a 753-residue protein that begins with a signal peptide and contains a 292-residue domain closely related to the catalytic modules of PC2, furin, and kex2. Within this region 58%, 65%, and 50% of the amino acids of PC3 are identical to those of the aligned PC2, furin, and kex2 sequences, respectively, and the catalytically important Asp, His, and Ser residues are all conserved. On Northern blots, PC3 hybridizes to two transcripts of 3 and 5 kilobases. Tissue distribution studies indicate that both PC2 and PC3 are expressed in a variety of neuroendocrine tissues, including pancreatic islets and brain, but are not expressed in liver, kidney, skeletal muscle, and spleen. The high degree of similarity of PC3, PC2, and furin suggests that they are all members of a superfamily of mammalian proteases that are involved in the processing of prohormones and/or other protein precursors. In contrast to furin, PC3, like PC2, lacks a hydrophobic transmembrane anchor, but it has a potential C-terminal amphipathic helical segment similar to the putative membrane anchor of carboxy-peptidase H. These and other differences suggest that these proteins carry out compartmentalized proteolysis within cells, such as processing within regulated versus constitutive secretory pathways.