Induction of epithelio-mesenchymal transformation of quail embryonic neural cells by inhibition of atypical protein kinase-C

Induction of epithelio-mesenchymal transformation of quail embryonic neural cells by inhibition of atypical protein kinase-C
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抑制非典型蛋白激酶-C诱导鹌鹑胚胎神经细胞上皮间质转化

DOI:
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发表时间:
1999
影响因子:
3.6
通讯作者:
D. Newgreen
D. Newgreen
中科院分区:
生物学3区
文献类型:
--
作者:
J. Minichiello;A. Ben;C. Hearn;B. Needham;D. Newgreen

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在体外培养的胚胎神经上皮中,蛋白激酶-c抑制剂可诱导细胞间质转化,其中包括细胞粘附分子和肌动蛋白骨架的重组。一种非抑制性类似物,BIM V和其他激酶的有效抑制剂没有活性。这表明了c激酶的核心作用,尽管强大的特异性c激酶抑制剂BIM I和Ro 31-8220的活性低于预期。几种激酶的共抑制不太可能解释这一点,因为当这些激酶与其他激酶的强效抑制剂联合使用时,不会发生增强。BIM I和Ro 31-8220仅强烈抑制常规钙调节的c激酶;这一点以及TMB-8缺乏抑制钙释放的作用,表明涉及新的和/或非典型亚型。常规和新型c -激酶的各种增强剂和激活剂单独作用不明显,不能降低staurosporine的作用,提示非典型c -激酶是关键。在Western blots上检测了E2胚胎神经组织中c -激酶亚型的存在,揭示了非典型亚型ι(或λ)和ζ以及α, γ, κ和μ亚型的免疫反应性。胚胎切片的免疫荧光定位显示,常规和新型异构体广泛分布,但只有非典型异构体λ和ζ在神经和其他上皮的顶端边缘富集;它们与细胞粘附分子n -钙粘蛋白和f -肌动蛋白重叠。因此,体外胚胎神经上皮上皮间质转化是通过抑制蛋白激酶活性诱导的,可能是通过非典型蛋白激酶c;非典型蛋白激酶- c亚型存在于组织的适当发育阶段和亚细胞部位的细胞能够上皮-间质转化。
Abstract Epithelio-mesenchymal transition, which involves the re-organisation of cell-cell adhesion molecules and the actin cytoskeleton, can be induced in embryonic neural epithelium in vitro by protein kinase-C inhibitors. A non-inhibitory analogue, BIM V, and potent inhibitors of other kinases are not active. This suggests a central role for C-kinases, although the powerful specific C-kinase inhibitors BIM I and Ro 31–8220 show lower than expected activity. Co-inhibition by several kinases is unlikely to account for this, since no potentiation occurs when these are combined with potent inhibitors of other kinases. BIM I and Ro 31–8220 strongly inhibit only conventional calcium-regulated C-kinases; this and the lack of effect of TMB-8, which inhibits calcium release, suggests that novel and/or atypical isoforms are involved. Various potentiators and activators of conventional and novel C-kinases have no obvious effect alone and fail to reduce the effect of staurosporine, suggesting that atypical C-kinases are critical. The presence of C-kinase isoforms in the E2 embryonic neural tissues has been probed on Western blots, revealing immunoreactivity for the atypical isoforms ι (or λ) and ζ and the α, γ, ɛ and μ isoforms. Immunofluorecent localisation on sections of embryos has shown the widespread distribution of conventional and novel isoforms but only the atypical isoforms λ and ζ are enriched at the apical margins of the neural and other epithelia; they overlap with the cell-cell adhesion molecule N-cadherin and with F-actin. Thus, epithelio-mesenchymal transition in the embryonic neural epithelium in vitro is induced by inhibiting protein kinase activity, probably via an atypical protein kinase-C; atypical protein kinase-C isoforms are present in the tissue at the appropriate developmental stage and subcellular site in cells capable of epithelio-mesenchymal transition.
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发表时间: 1991
影响因子: 11.1
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发表时间: 1992-11-06
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