Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2
Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2
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DOI：
10.1006/excr.1999.4738
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发表时间：
2000-01-10
影响因子：
3.7
通讯作者：
Hamaguchi, M
中科院分区：
文献类型：
--
作者：
Kurata, H;Thant, AA;Hamaguchi, M
我们利用结构型活性/显性阴性形式的MEK1和MEK1特异性抑制物研究了MEK1信号在基质金属蛋白酶-2激活中的作用。我们发现，带有活性形式的MEK1的细胞转化显著增加了细胞分泌和蛋白分解激活的基质金属蛋白酶-2，从而刺激了细胞的侵袭性，相反，在v-src转化的细胞和conA激活的细胞中，显性阴性形式的MEK1的表达导致了对基质金属蛋白酶-2的分泌和蛋白分解激活的抑制，此外，用MEK1特异性抑制剂PD98059处理的转化细胞强烈地抑制了基质金属蛋白酶-8的分泌和激活，而用PI3激酶抑制剂wortmannin处理后，对基质金属蛋白酶-8的分泌和激活没有明显的影响。综上所述，这些结果有力地表明，MEK-MAP激酶信号，而不是PI3激酶信号，在激活MMP-8分泌以及随后在v-src转化细胞的侵袭性中发挥关键作用。(C)2000年学术出版社。
We investigated the role of MEK1 signaling in MMP-2 activation by use of constitutive active/dominant negative forms of MEK1 and MEK1-specific inhibitor. We found that cell transformation with active forms of MEK1 dramatically increased secretion and proteolytic activation of MMP-2 and subsequently stimulated invasiveness of cells, Contrary, expression of dominant negative form of MEK1 in v-src-transformed cells or in Con A-activated cells resulted in the suppression of the augmented secretion and proteolytic activation of MMP-2, In addition, treatment of v-src-transformed cells with PD98059, a MEK1-specific inhibitor, strongly suppressed the secretion and activation of MMP-8, whereas treatment with wortmannin, a PI3 kinase inhibitor, showed no clear effect on MMP-8 secretion. Taken together, these results strongly suggest that MEK-MAP kinase signaling, but not PI3 kinase signaling, plays a critical role in the activation of MMP-8 secretion and, subsequently, in the invasiveness of v-src-transformed cells. (C) 2000 Academic Press.