Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Science. 2012 Dec 7;338(6112):1337-40. doi: 10.1126/science.1228734. Epub 2012 Nov 8.
Despite more than 30 years of work on the Wnt signaling pathway, the basic mechanism of how the extracellular Wnt signal increases the intracellular concentration of β-catenin is still contentious. Circumventing much of the detailed biochemistry, we used basic principles of chemical kinetics coupled with quantitative measurements to define the reactions on β-catenin directly affected by the Wnt signal. We conclude that the core signal transduction mechanism is relatively simple, with only two regulated phosphorylation steps. Their partial inhibition gives rise to the full dynamics of the response and subsequently maintains a steady state in which the concentration of β-catenin is increased.
尽管人们对 Wnt 信号通路进行了 30 多年的研究,但细胞外 Wnt 信号如何增加 β-连环蛋白的细胞内浓度的基本机制仍存在争议。我们绕过了大部分详细的生物化学内容,而是使用化学动力学的基本原理和定量测量来直接定义受 Wnt 信号影响的 β-连环蛋白的反应。我们的结论是,核心信号转导机制相对简单,只有两个受调控的磷酸化步骤。它们的部分抑制会引起反应的全动力学,随后维持一个β-连环蛋白浓度增加的稳定状态。
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