Martin-Vandelet N, Paris S, Bourguignon J, Sesboüé R, Martin J P, Diarra-Mehrpour M
Laboratoire de Physiopathologie et Génétique Rénale et Pulmonaire, Insitut National de la Santé et de la Recherche Médicale,INSERM Unité 295, France.
Eur J Biochem. 1999 Jan;259(1-2):476-84. doi: 10.1046/j.1432-1327.1999.00067.x.
The inter-alpha-trypsin inhibitor (ITI) family is a group of structurally related plasma serine protease inhibitors. The ITI family members consist of combinations of mature heavy chains named HC1, HC2, HC3 linked to bikunin (a Kunitz-type protease inhibitor) by a covalent interchain protein-glycosaminoglycan-protein cross-link. The biosynthesis of the ITI family members takes place in the liver. In this report we examine the biosynthesis of these proteins using transient transfected COS-7 cells expressing one or more combinations of human ITI chains. The processing and secretion of alpha1-microglobulin and bikunin does not require the ITI heavy chains. A small proportion of the H3 chain seems to be processed into the HC3 form in the absence of the other ITI chains. In contrast, the processing of H2 into HC2 needs the presence of the L chain. The COS-7 cells are able to link the HC2 and HC3 heavy chains with bikunin by means of a chondroitin sulfate bridge, and thus to generate 260-kDa ITI-like proteins as well as pre-alpha-trypsin inhibitor (PalphaI). However, the maturation of the Hl chain into HC1 and the assembly of HC1 inside multichain proteins may take place according to a mechanism which differs from that of the H2 and H3 chains. These results indicate that the assembly of the constituent chains of the ITI-like proteins and PalphaI is not dependent on the liver machinery.
α-胰蛋白酶抑制剂（ITI）家族是一组结构相关的血浆丝氨酸蛋白酶抑制剂。ITI家族成员由成熟重链HC1、HC2、HC3的组合构成，这些重链通过链间蛋白-糖胺聚糖-蛋白共价交联与比基尼（一种库尼茨型蛋白酶抑制剂）相连。ITI家族成员的生物合成在肝脏中进行。在本报告中，我们使用瞬时转染表达一种或多种人ITI链组合的COS-7细胞来研究这些蛋白质的生物合成。α1-微球蛋白和比基尼的加工与分泌不需要ITI重链。在没有其他ITI链的情况下，一小部分H3链似乎会加工成HC3形式。相反，H2加工成HC2需要L链的存在。COS-7细胞能够通过硫酸软骨素桥将HC2和HC3重链与比基尼相连，从而生成260 kDa的ITI样蛋白以及前α-胰蛋白酶抑制剂（PαI）。然而，H1链成熟为HC1以及HC1在多链蛋白内的组装可能通过一种不同于H2和H3链的机制进行。这些结果表明，ITI样蛋白和PαI的组成链的组装不依赖于肝脏机制。
