Furin Functions as a Nonproteolytic Chaperone for Matrix Metalloproteinase-28: MMP-28 Propeptide Sequence Requirement.
Furin Functions as a Nonproteolytic Chaperone for Matrix Metalloproteinase-28: MMP-28 Propeptide Sequence Requirement.
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DOI：
10.1155/2011/630319
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发表时间：
2011
影响因子：
3
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
Pavlaki M;Zucker S;Dufour A;Calabrese N;Bahou W;Cao J
尽管 MMP-28 参与许多重要的生理和病理状况，但这种分泌性蛋白酶的作用机制尚不清楚。我们现在已经证明，弗林蛋白酶通过与 MMP-28 的前肽结构域相互作用，充当 MMP-28 分泌的分子间伴侣。使用用MMP-28 cDNA转染的COS-1细胞，与细胞裂解物相比，条件培养基中MMP-28的蛋白质水平相当低。 MMP-28 与弗林蛋白酶 cDNA 共表达导致 MMP-28 分泌显着增强。与预期相反，弗林蛋白酶共有序列处的 MMP-28 裂解并未发生，并且蛋白水解无活性弗林蛋白酶在增强 MMP-28 分泌方面同样有效。弗林蛋白酶和 MMP-28 共免疫沉淀并部分共免疫定位于转染细胞的细胞质中。与弗林蛋白酶 cDNA 共转染也增强了 MMP-28 诱导的细胞迁移。总之，我们的数据提供了 MMP-28 在细胞中发挥功能的新机制，其中弗林蛋白酶充当分子间伴侣。
Although MMP-28 is involved in numerous important physiologic and pathologic conditions, the mechanisms of action of this secreted proteinase is not well understood. We now have demonstrated that furin serves as an intermolecular chaperone for MMP-28 secretion by interacting with the propeptide domain of MMP-28. Employing COS-1 cells transfected with MMP-28 cDNA, protein levels of MMP-28 were quite low in conditioned media as compared to cell lysates. Coexpression of MMP-28 with furin cDNA resulted in markedly enhanced MMP-28 secretion. Contrary to expectation, cleavage of MMP-28 at the furin consensus sequence did not occur and proteolytic inactive furin was equally effective in enhancing MMP-28 secretion. Furin and MMP-28 coimmunoprecipitated and were partially coimmunolocalized in the cytoplasm of transfected cells. Cotransfection with furin cDNA also enhanced MMP-28 induced cell migration. In conclusion, our data provide a novel mechanism for MMP-28 function in cells in which furin serves as an intermolecular chaperone.