CK2 目标位点的底物质量对其功能和进化具有决定性作用。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-06-10 DOI:10.1016/j.cels.2024.05.005
David Bradley, Chantal Garand, Hugo Belda, Isabelle Gagnon-Arsenault, Moritz Treeck, Sabine Elowe, Christian R Landry
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引用次数: 0

摘要

大多数生物过程都是由与短线性基团结合的信号模块调控的。对于蛋白激酶来说,底物可能与激酶识别基序完全匹配,也可能仅部分匹配,这种特性被称为 "底物质量"。然而,目前还不清楚底物质量的差异是代表中性变异还是具有功能性后果。我们研究了具有多种基本功能的激酶 CK2 的这一问题。我们的研究表明,最佳 CK2 位点以最大的化学计量单位磷酸化,并且在许多条件下都能发现,而最小底物的磷酸化程度较弱,并且具有调节功能。最佳 CK2 位点往往更为保守,底物的质量往往通过选择来调整。对于中间位点,底物质量的增加或降低可能是有害的,正如我们在研究动核上的 CK2 底物时所证明的那样。这些结果共同表明,底物质量在磷酸根功能和进化中发挥着重要作用。补充信息中包含了本文透明的同行评审过程记录。
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The substrate quality of CK2 target sites has a determinant role on their function and evolution.

Most biological processes are regulated by signaling modules that bind to short linear motifs. For protein kinases, substrates may have full or only partial matches to the kinase recognition motif, a property known as "substrate quality." However, it is not clear whether differences in substrate quality represent neutral variation or if they have functional consequences. We examine this question for the kinase CK2, which has many fundamental functions. We show that optimal CK2 sites are phosphorylated at maximal stoichiometries and found in many conditions, whereas minimal substrates are more weakly phosphorylated and have regulatory functions. Optimal CK2 sites tend to be more conserved, and substrate quality is often tuned by selection. For intermediate sites, increases or decreases in substrate quality may be deleterious, as we demonstrate for a CK2 substrate at the kinetochore. The results together suggest a strong role for substrate quality in phosphosite function and evolution. A record of this paper's transparent peer review process is included in the supplemental information.

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