Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3
Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3
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DOI：
10.1002/dvdy.20227
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发表时间：
2005-03-01
影响因子：
2.5
通讯作者：
de Celis, JF
中科院分区：
文献类型：
--
作者：
Gómez, AR;López-Varea, A;de Celis, JF
细胞外信号调节激酶(ERK)是表皮生长因子受体(EGFR)和成纤维细胞生长因子受体(FGFR)信号通路的关键转导分子，在动物发育的多个过程中都需要它的功能。ERK的活性依赖于保守的苏氨酸和酪氨酸残基的磷酸化状态，这种状态受不同的激酶和磷酸酶的调节。在ERK(双特异性磷酸酶)中，一类对苏氨酸和酪氨酸残基具有特异性的磷酸酶在其去磷酸化和随后的失活中起着保守的作用。在这里，我们表征了双特异性磷酸酶MKP3在果蝇EGFR和非洲爪哇FGFR信号转导中的作用。MKP3在果蝇翼静脉形成和非洲爪哇前后神经构型过程中起重要作用。我们发现MKP3基因的表达定位于高EGFR和FGFR信号转导部位。此外，MKP3在果蝇和非洲爪哇中的表达依赖于ERK的功能，这表明MKP3在Ras/ERK信号通路的活性上构成了一个保守的负反馈环。(C)2005年Wiley-Liss，Inc.
The extracellular signal-regulated kinase (ERK) is a key transducer of the epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) signaling pathways, and its function is required in multiple processes during animal development. The activity of ERK depends on the phosphorylation state of conserved threonine and tyrosine residues, and this state is regulated by different kinases and phosphatases. A family of phosphatases with specificity toward both threonine and tyrosine residues in ERK (dual-specificity phosphatases) play a conserved role in its dephosphorylation and consequent inactivation. Here, we characterize the function of the dual-specificity phosphatase MKP3 in Drosophila EGFR and Xenopus FGFR signaling. The function of MKP3 is required during Drosophila wing vein formation and Xenopus anteroposterior neural patterning. We find that the expression of the MKP3 gene is localized in places of high EGFR and FGFR signaling. Furthermore, this restricted expression depends on ERK function both in Drosophila and Xenopus, suggesting that MKP3 constitutes a conserved negative feedback loop on the activity of the Ras/ERK signaling pathway. (C) 2005 Wiley-Liss, Inc.