Fu Accalia, Screaton Robert A
Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Cell Cycle. 2008 Dec 15;7(24):3823-8. doi: 10.4161/cc.7.24.7241. Epub 2008 Dec 21.
The classical role of AMP-activated protein kinase (AMPK) as an energy status sensor is expanding to include other members of the AMPK family. Recent genetic and cell biological evidence points to a role for MAP/microtubule affinity-regulating kinase 2 (MARK2/EMK/Par1b) in the regulation of metabolic events as well as in the control of CREB-dependent transcription activated by glucose in pancreatic islet beta cells. We have recently developed an in vitro kinase screening platform to identify novel kinase:substrate pairs, the building blocks of signal transduction pathways. Application of this technology led us to identify MARK2 as the kinase that targets a novel glucose-regulated phosphorylation site on Transducer of Regulated CREB Activity 2 (TORC2, referred to as CREB-Regulated Transcriptional Coactivator 2, or CRTC2), a transcriptional coactivator essential for CREB activity in beta cells. We discuss these recent developments and suggest a model whereby members of the AMPK family integrate numerous signals to coordinate energy metabolism and cellular polarity with gene expression to regulate cell function/proliferation.
AMP 激活的蛋白激酶（AMPK）作为能量状态传感器的经典作用正在扩展，以纳入 AMPK 家族的其他成员。最近的遗传学和细胞生物学证据表明，丝裂原活化蛋白激酶/微管亲和力调节激酶 2（MARK2/EMK/Par1b）在调节代谢事件以及控制胰岛β细胞中由葡萄糖激活的 CREB 依赖性转录方面发挥作用。我们最近开发了一种体外激酶筛选平台，以识别新型激酶：底物对，即信号转导途径的组成部分。应用这项技术使我们确定 MARK2 为靶向调节 CREB 活性转导子 2（TORC2，也称为 CREB 调节转录共激活因子 2 或 CRTC2）上一个新的葡萄糖调节磷酸化位点的激酶，TORC2 是β细胞中 CREB 活性所必需的转录共激活因子。我们讨论这些最新进展，并提出一个模型，即 AMPK 家族成员整合多种信号，以协调能量代谢和细胞极性与基因表达，从而调节细胞功能/增殖。
