Covalent interaction between proform of eosinophil major basic protein (proMBP) and pregnancy-associated plasma protein-A (PAPP-A) is a cell-mediated event and required for proMBP inhibition of the catalytic activity of PAPP-A.

Covalent interaction between proform of eosinophil major basic protein (proMBP) and pregnancy-associated plasma protein-A (PAPP-A) is a cell-mediated event and required for proMBP inhibition of the catalytic activity of PAPP-A.
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嗜酸性粒细胞主要碱性蛋白原体 (proMBP) 与妊娠相关血浆蛋白 A (PAPP-A) 之间的共价相互作用是细胞介导的事件,是 proMBP 抑制 PAPP-A 催化活性所必需的。

DOI:
10.1016/j.abb.2004.01.005
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发表时间:
2004
期刊:
Archives of biochemistry and biophysics.
影响因子:
--
通讯作者:
Qin,Xuezhong
Qin,Xuezhong
中科院分区:
--
文献类型:
--
作者:
Sivanandam,ArunS;Mohan,Subburaman;Kapur,Sanjay;Kita,Hirohito;Lau,K-HWilliam;Bagi,Gyorgy;Baylink,DavidJ;Qin,Xuezhong

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本研究旨在探讨嗜酸性粒细胞主要碱性蛋白(ProMBP)前体抑制妊娠相关血浆蛋白(PAPP)-A的IGFBP-4蛋白分解活性的机制。在293T细胞中过表达PAPP-A和proMBP,或分别过表达proMBP和PAPP-A可形成共价的proMBP-PAPP-A复合体,并抑制IGFBP-4的蛋白降解。当重组proMBP和PAPP-A与U2骨肉瘤细胞共同孵育或将重组proMBP加入过表达PAPP-A的U2细胞中时,也得到了类似的结果。相反,重组proMBP和PAPP-A在无细胞条件下孵育时没有形成共价的proMBP-PAPP-A复合体,也没有抑制IGFBP-4的蛋白降解,尽管proMBP能够以非共价的方式与PAPP-A相互作用。这些新的发现表明,形成共价的proMBP-PAPP-A复合体是一种细胞介导的事件,是proMBP抑制PAPP-A催化活性所必需的。
This study was undertaken to determine the mechanism by which proform of eosinophil major basic protein (proMBP) inhibits the IGFBP-4 proteolytic activity of pregnancy-associated plasma protein (PAPP)-A. Co-overexpression of PAPP-A with proMBP in 293T cells, or co-incubation of 293T cells, respectively, overexpressing proMBP and PAPP-A resulted in the formation of a covalent proMBP–PAPP-A complex and inhibition of IGFBP-4 proteolysis. Similar results were obtained when recombinant proMBP and PAPP-A were incubated in the presence of U2 osteosarcoma cells or when recombinant proMBP was added to the U2 cells overexpressing PAPP-A. In contrast, no formation of covalent proMBP–PAPP-A complex or inhibition of IGFBP-4 proteolysis was observed when recombinant proMBP and PAPP-A were incubated under cell-free conditions, although proMBP was able to interact with PAPP-A in a non-covalent manner. These new findings suggest that formation of covalent proMBP–PAPP-A complex is a cell-mediated event and is required for proMBP to inhibit the catalytic activity of PAPP-A.