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首页> 外文期刊>Molecular and Cellular Biology >Low-Molecular-Weight Protein Tyrosine Phosphatase Is a Positive Component of the Fibroblast Growth Factor Receptor Signaling Pathway
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Low-Molecular-Weight Protein Tyrosine Phosphatase Is a Positive Component of the Fibroblast Growth Factor Receptor Signaling Pathway

机译：低分子量蛋白酪氨酸磷酸酶是成纤维细胞生长因子受体信号通路的积极组成部分

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Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including platelet-derived growth factor and epidermal growth factor. Here we identify the Xenopus laevis homolog of LMW-PTP1 (XLPTP1) as an additional positive regulator in the fibroblast growth factor (FGF) signaling pathway during Xenopus development. XLPTP1 has an expression pattern that displays substantial overlap with FGF receptor 1 (FGFR1) during Xenopus development. Using morpholino antisense technology, we show that inhibition of endogenous XLPTP1 expression dramatically restricts anterior and posterior structure development and inhibits mesoderm formation. In ectodermal explants, loss of XLPTP1 expression dramatically blocks the induction of the early mesoderm gene, Xbrachyury (Xbra), by FGF and partially blocks Xbra induction by Activin. Moreover, FGF-induced activation of mitogen-activated protein (MAP) kinase is also inhibited by XLPTP1 morpholino antisense oligonucleotides; however, introduction of RNA encoding XLPTP1 is able to rescue morphological and biochemical effects of antisense inhibition. Inhibition of FGF-induced MAP kinase activity due to loss of XLPTP1 is also rescued by an active Ras, implying that XLPTP1 may act upstream of or parallel to Ras. Finally, XLPTP1 physically associates only with an activated FGFR1, and this interaction requires the presence of SNT1/FRS-2 (FGFR substrate 2). Although LMW-PTP1 has been shown to participate in other receptor systems, the data presented here also reveal XLPTP1 as a new and important component of the FGF signaling pathway.
机译：低分子量蛋白酪氨酸磷酸酶（LMW-PTP）已参与调节细胞生长和肌动蛋白重排的调节，这些细胞和肌动蛋白重排由几种受体酪氨酸激酶介导，包括血小板衍生的生长因子和表皮生长因子。在这里，我们确定LMW-PTP1（XLPTP1）的非洲爪蟾同源物是非洲爪蟾发育过程中成纤维细胞生长因子（FGF）信号通路中的一个额外的正调节剂。 XLPTP1的表达模式在非洲爪蟾（Xenopus）发育过程中与FGF受体1（FGFR1）基本上重叠。使用吗啉代反义技术，我们表明抑制内源性XLPTP1表达大大限制了前后结构的发展，并抑制了中胚层的形成。在外胚层外植体中，XLPTP1表达的丧失极大地阻碍了FGF对早期中胚层基因 Xbrachyury （ Xbra ）的诱导，部分阻止了 Xbra 激活素诱导。此外，XLPTP1吗啉代反义寡核苷酸也抑制了FGF诱导的丝裂原活化蛋白（MAP）激酶的活化。然而，引入编码XLPTP1的RNA能够挽救反义抑制的形态和生化作用。由于XLPTP1的丧失而导致的FGF诱导的MAP激酶活性的抑制也可以通过活跃的Ras来挽救，这意味着XLPTP1可能在Ras的上游或与之平行。最后，XLPTP1仅与激活的FGFR1物理关联，并且这种相互作用需要SNT1 / FRS-2（FGFR底物2）的存在。尽管已显示LMW-PTP1参与其他受体系统，但此处提供的数据也显示XLPTP1是FGF信号通路的新的重要组成部分。

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