Bacteria possess diverse classes of signaling systems that they use to sense and respond to their environments and execute properly timed developmental transitions. One widespread and evolutionarily ancient class of signaling systems are the Hanks-type Ser/Thr kinases, also sometimes termed “eukaryotic-like” due to their homology with eukaryotic kinases. In diverse bacterial species, these signaling systems function as critical regulators of general cellular processes such as metabolism, growth and division, developmental transitions such as sporulation, biofilm formation, and virulence, as well as antibiotic tolerance. This multifaceted regulation is due to the ability of a single Hanks-type Ser/Thr kinase to post-translationally modify the activity of multiple proteins, resulting in the coordinated regulation of diverse cellular pathways. However, in part due to their deep integration with cellular physiology, to date, we have a relatively limited understanding of the timing, regulatory hierarchy, the complete list of targets of a given kinase, as well as the potential regulatory overlap between the often multiple kinases present in a single organism. In this review, we discuss experimental methods and curated datasets aimed at elucidating the targets of these signaling pathways and approaches for using these datasets to develop computational models for quantitative predictions of target motifs. We emphasize novel approaches and opportunities for collecting data suitable for the creation of new predictive computational models applicable to diverse species.

中文翻译：

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细菌Hanks型Ser/Thr信号系统调控靶点的实验测量和计算预测

细菌拥有多种信号系统，它们用来感知和响应环境，并执行适当时机的发育转变。Hanks 型 Ser/Thr 激酶是一类广泛存在且进化上古老的信号系统，由于与真核激酶同源，有时也称为“类真核”。在不同的细菌物种中，这些信号系统作为一般细胞过程的关键调节器，例如新陈代谢、生长和分裂、孢子形成等发育转变、生物膜形成和毒力，以及抗生素耐受性。这种多方面的调节是由于单个 Hanks 型 Ser/Thr 激酶能够翻译后修饰多种蛋白质的活性，从而协调调节不同的细胞途径。然而，部分由于它们与细胞生理学的深度整合，迄今为止，我们对时间、监管层次、给定激酶的完整靶标列表以及通常多个激酶之间潜在的监管重叠的了解相对有限。激酶存在于单一生物体中。在这篇综述中，我们讨论了旨在阐明这些信号通路目标的实验方法和精选数据集，以及使用这些数据集开发用于目标基序定量预测的计算模型的方法。我们强调收集适合创建适用于不同物种的新预测计算模型的数据的新方法和机会。