Human high molecular weight kininogen binds to human umbilical vein endothelial cells via its heavy and light chains.
Human high molecular weight kininogen binds to human umbilical vein endothelial cells via its heavy and light chains.
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人高分子量激肽原通过其重链和轻链与人脐静脉内皮细胞结合。
DOI：
10.1182/blood.v81.5.1306.1306
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发表时间：
1993
期刊：
影响因子：
20.3
通讯作者：
Allen P. Kaplan
中科院分区：
文献类型：
--
作者：
S. Reddigari;Piotr Kuna;G. Miragliotta;Y. Shibayama;K. Nishikawa;Allen P. Kaplan
高分子量激肽原(HK)是一种多功能的血浆糖蛋白，在连接炎症和凝血的通路中占有重要地位。血浆激肽释放酶切除血管活性多肽缓激肽，得到无激动素的HK，它由一个65-kD的N-末端重链(HK-HC)通过二硫键连接到C-末端的45-kD轻链(HK-LC)。HK-HC是SH-蛋白水解酶的抑制剂，HK-LC含有凝血因子、前激肽释放酶和凝血因子XI的结合部位。此前研究表明，HK通过一类高亲和力结合位点以锌离子依赖的方式与人脐静脉内皮细胞(HUVEC)特异性结合。为了确定HK的细胞结合区，我们进一步表征了这种相互作用。竞争结合实验表明，HK-LC和HK-HC均能抑制标记HK的结合，其半数抑制浓度(IC_(50))分别为77nmol/L和89nmol/L。裂解的双链HK(Hka)的IC50为73nmol/L，而未裂解的HK的IC50为335nmol/L。直接结合实验表明，HUVEC以锌(2+)依赖的方式与纯化的[125I]HK-HC和[125I]HK-LC结合，HK-LC不取代结合的HK-HC。HK的低分子激肽原轻链或前激肽释放酶结合区不抑制HK与HUVEC的结合。因此，我们的结果表明：(1)HK能够通过重链和轻链与内皮细胞结合，(2)Hka与HUVEC有较高的亲和力，(3)纯化的重链和轻链能够直接与HUVEC结合。这些数据与内皮细胞上HK的单一高亲和力位点的存在是一致的，在该位点内有与重链和轻链结合的亚位点。
High molecular weight kininogen (HK) is a multifunctional plasma glycoprotein that occupies a critical position in pathways that link inflammation and coagulation. Excision of the vasoactive peptide bradykinin by plasma kallikrein results in kinin-free HK that consists of a 65-Kd N-terminal heavy chain (HK-HC) linked to the C-terminal 45-Kd light chain (HK-LC) by a disulfide bridge. HK-HC is an inhibitor of SH-proteases and HK-LC contains the binding sites for coagulation cofactors prekallikrein and factor XI. HK has previously been shown to bind specifically to human umbilical vein endothelial cells (HUVEC) in a zinc(2+)-dependent manner by a single class of high-affinity binding sites. We have further characterized that interaction in order to determine the cell-binding regions of HK. Competition binding experiments have indicated that either HK-LC or HK-HC was able to inhibit the binding of labeled HK with a 50% inhibitory concentration (IC50) of 77 nmol/L and 89 nmol/L, respectively. Cleaved two-chain HK (HKa) had an IC50 of 73 nmol/L, whereas uncleaved HK had an IC50 of 335 nmol/L. Direct binding experiments have indicated that HUVEC bind both purified [125I]HK-HC and [125I]HK-LC in a zinc(2+)-dependent manner and that HK-LC did not displace bound HK-HC. The light chain of low molecular weight kininogen or prekallikrein-binding region of HK did not inhibit the binding of HK to HUVEC. Our results, therefore, indicate that (1) HK is capable of binding to endothelial cells via both heavy and light chain moieties, (2) HKa has a higher affinity to HUVEC, and (3) purified heavy and light chains are capable of directly binding to HUVEC. The data are consistent with the presence of a single high-affinity site for HK on endothelial cells within which are subsites that bind to heavy and light chains.
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美国病理学家协会主席致辞。
DOI：
--
发表时间：
1987
期刊：
The American journal of pathology
影响因子：
--
作者：
Cotran,RS
通讯作者：
Cotran,RS
激肽原的结构域 3 包含一个细胞结合位点和一个修饰血小板凝血酶活化的位点。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jiang,YP;Muller-Esterl,W;Schmaier,AH
通讯作者：
Schmaier,AH
DOI：
10.1016/s0021-9258(18)37596-3
发表时间：
1988-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Alvin H. Schmaier;A. Kuo;D. Lundberg;S. Murray;D. Cines
通讯作者：
Alvin H. Schmaier;A. Kuo;D. Lundberg;S. Murray;D. Cines
高分子量激肽原通过其重链和轻链与血小板结合，结合后会改变激肽释放酶裂解的敏感性。
影响因子：
20.3
作者：
Meloni,FJ;Gustafson,EJ;Schmaier,AH
通讯作者：
Schmaier,AH
低分子量激肽原与血小板结合，调节凝血酶诱导的血小板活化。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Meloni,FJ;Schmaier,AH
通讯作者：
Schmaier,AH