A casual decision made one evening in 1976, in a bar near the Biochemistry Department at the University of Dundee, led me to start my personal research journey by following up a paper that suggested that acetyl-CoA carboxylase (ACC) (believed to be a key regulatory enzyme of fatty acid synthesis) was inactivated by phosphorylation by what appeared to be a novel, cyclic AMP-independent protein kinase. This led me to define and name the AMP-activated protein kinase (AMPK) signalling pathway, on which I am still working 46 years later. ACC was the first known downstream target for AMPK, but at least 100 others have now been identified. This article contains some personal reminiscences of that research journey, focussing on: (i) the early days when we were defining the kinase and developing the key tools required to study it; (ii) the late 1990s and early 2000s, an exciting time when we and others were identifying the upstream kinases; (iii) recent times when we have been studying the complex role of AMPK in cancer. The article is published in conjunction with the Sir Philip Randle Lecture of the Biochemical Society, which I gave in September 2022 at the European Workshop on AMPK and AMPK-related kinases in Clydebank, Scotland. During the early years of my research career, Sir Philip acted as a role model, due to his pioneering work on insulin signalling and the regulation of pyruvate dehydrogenase.

中文翻译：

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AMP 活化蛋白激酶——从 1 到 100 个下游目标的旅程

1976 年的一个晚上，在邓迪大学生物化学系附近的一家酒吧里，一个偶然的决定让我开始了我的个人研究之旅，跟进了一篇论文，该论文表明乙酰辅酶 A 羧化酶 (ACC)（被认为是一种脂肪酸合成的关键调节酶）被似乎是一种新型的、环状 AMP 独立的蛋白激酶磷酸化而失活。这促使我定义并命名了 AMP 活化蛋白激酶 (AMPK) 信号通路，46 年后我仍在研究该通路。ACC 是 AMPK 的第一个已知下游目标，但现在至少已经确定了 100 个其他目标。这篇文章包含了那次研究之旅的一些个人回忆，重点是：(i) 我们定义激酶和开发研究它所需的关键工具的早期；(ii) 1990 年代末和 2000 年代初，这是我们和其他人确定上游激酶的激动人心的时期；(iii) 最近我们一直在研究 AMPK 在癌症中的复杂作用。这篇文章与 Philip Randle 爵士的生化学会讲座一起发表，我于 2022 年 9 月在苏格兰克莱德班克举行的关于 AMPK 和 AMPK 相关激酶的欧洲研讨会上发表了这篇演讲。在我研究生涯的早期，由于他在胰岛素信号传导和丙酮酸脱氢酶调节方面的开创性工作，菲利普爵士成为了榜样。这是我于 2022 年 9 月在苏格兰克莱德班克举行的关于 AMPK 和 AMPK 相关激酶的欧洲研讨会上发表的。在我研究生涯的早期，由于他在胰岛素信号传导和丙酮酸脱氢酶调节方面的开创性工作，菲利普爵士成为了榜样。这是我于 2022 年 9 月在苏格兰克莱德班克举行的关于 AMPK 和 AMPK 相关激酶的欧洲研讨会上发表的。在我研究生涯的早期，由于他在胰岛素信号传导和丙酮酸脱氢酶调节方面的开创性工作，菲利普爵士成为了榜样。