The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development.

The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development.
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DOI:
10.1083/jcb.200705035
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发表时间:
2007-09-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Khew-Goodall Y
Khew-Goodall Y
中科院分区:
其他
文献类型:
--
作者:
Wyatt L;Wadham C;Crocker LA;Lardelli M;Khew-Goodall Y

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上皮-间充质转化(EMT)在胚胎发育过程中对新组织和器官的形成至关重要,也被认为是癌症转移的先决条件。我们在这里报道了蛋白酪氨酸磷酸酶PEZ在斑马鱼胚胎发育中的大脑、心脏、咽弓和体节的离散位置瞬时表达。我们还发现,PEZ基因敲除导致了这些器官的缺陷,表明在器官发生中发挥了关键作用。上皮MDCK细胞中PEZ的过表达导致EMT,细胞形态和功能发生剧烈变化,伴随着EMT典型的基因表达的变化。PEZ基因可诱导转化生长因子β信号转导,在发育过程中起关键作用,在肿瘤发生过程中也可能发挥作用。在斑马鱼中,转化生长因子β-3与PEZ在许多组织中共表达,当PEZ表达被下调时,这些组织中的转化生长因子BMP-3就失去了表达。综上所述,我们的数据表明,PEZ通过诱导转化生长因子β和EMT在器官发生中发挥关键作用。
Epithelial–mesenchymal transition (EMT), crucial during embryogenesis for new tissue and organ formation, is also considered to be a prerequisite to cancer metastasis. We report here that the protein tyrosine phosphatase Pez is expressed transiently in discrete locations in developing brain, heart, pharyngeal arches, and somites in zebrafish embryos. We also find that Pez knock-down results in defects in these organs, indicating a crucial role in organogenesis. Overexpression of Pez in epithelial MDCK cells causes EMT, with a drastic change in cell morphology and function that is accompanied by changes in gene expression typical of EMT. Transfection of Pez induced TGFβ signaling, critical in developmental EMT with a likely role also in oncogenic EMT. In zebrafish, TGFβ3 is co- expressed with Pez in a number of tissues and its expression was lost from these tissues when Pez expression was knocked down. Together, our data suggest Pez plays a crucial role in organogenesis by inducing TGFβ and EMT.
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