Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts

Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts
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DOI:
10.1016/j.febslet.2007.11.036
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发表时间:
2007-12-22
期刊:
影响因子:
3.5
通讯作者:
Nikawa, Takeshi
Nikawa, Takeshi
中科院分区:
生物学3区
文献类型:
--
作者:
Furochi, Harumi;Tamura, Seiko;Nikawa, Takeshi

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完整的骨活性素是一种新型 I 型膜糖蛋白,在 C2C12 成肌细胞的近膜区域的二碱基基序处脱落。细胞外片段通过假定的金属蛋白酶分泌到培养基中。骨激活素的细胞外片段(而非对照蛋白)诱导 NIH-3T3 成纤维细胞中基质金属蛋白酶 3 (MMP-3) 的表达。表皮生长因子 (ERK) 激酶抑制剂抑制骨激活素介导的 MMP-3 表达,而骨激活素的细胞外片段则激活丝裂原激活蛋白激酶途径中的 ERK1/2 和 p38。我们的结果表明,脱落产生的骨激活素细胞外片段可作为生长因子,通过成纤维细胞中的 ERK 途径诱导 MMP-3 表达。 (C) 2007 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.