Sp1 phosphorylation by Erk 2 stimulates DNA binding
Sp1 phosphorylation by Erk 2 stimulates DNA binding
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DOI：
10.1006/bbrc.1998.9964
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发表时间：
1999-01-19
影响因子：
3.1
通讯作者：
Todisco, A
中科院分区：
文献类型：
--
作者：
Merchant, JL;Du, M;Todisco, A
EGF通过多种信号转导途径刺激基因表达，包括ras-Erk途径。我们以前已经表明，EGF受体激活刺激胃泌素基因表达，通过富含GC的元素称为gERE。该元件结合Sp1家族成员，并提高了ras-Erk信号转导级联可能靶向这种新的EGF响应元件的可能性。此外，已知Erk 2能够磷酸化其他促分裂原诱导的转录因子，例如，Elk，Sap表明Erk也可以诱导磷酸化Sp1。为了直接使用共转染实验来验证这一假设，我们证明ras和Erk 2激活确实靶向gERE元件。Mek 1激酶抑制剂PD 98059可阻断50%的EGF诱导型胃泌素启动子活性。用重组Erk 2预处理提取物刺激Sp1结合，而去磷酸化减少但不消除Sp1结合。总之，这些研究证明了新的发现，诱导型结合的Sp1的磷酸化状态进行调节。此外，胃泌素启动子激活部分由靶向Sp1的ras-Erk信号级联介导。(C)北京：科学出版社.
EGF stimulates gene expression through a variety of signal transduction pathways that include the ras-Erk pathway. We have shown previously that EGF receptor activation stimulates gastrin gene expression through a GC-rich element called gERE. This element binds Sp1 family members and raises the possibility that the ras-Erk signal transduction cascade may target this novel EGF responsive element. Moreover, it is known that Erk 2 is capable of phosphorylating other mitogen-inducible transcription factors, e.g., Elk, Sap suggesting that Erk may also inducibly phosphorylate Sp1. To test this hypothesis directly using cotransfection experiments, we show that ras and Erk 2 activation indeed target the gERE element. The Mek 1 kinase inhibitor, PD98059, blocks 50% of EGF-inducible gastrin promoter activity. Pretreatment of the extracts with recombinant Erk2 stimulated Sp1 binding; whereas dephosphorylation reduced but did not eliminate Sp1 binding. Together, these studies demonstrate the novel finding that inducible binding of Sp1 is regulated by its state of phosphorylation. Further, gastrin promoter activation is mediated in part by the ras-Erk signaling cascade that targets Sp1. (C) 1999 Academic Press.