Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei, 230032, China.
Department of Oncology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Acta Pharmacol Sin. 2018 Nov;39(11):1699-1705. doi: 10.1038/s41401-018-0049-z. Epub 2018 Jun 19.
G protein-coupled receptor kinases (GRKs) constitute seven subtypes of serine/threonine protein kinases that specifically recognize and phosphorylate agonist-activated G protein-coupled receptors (GPCRs), thereby terminating the GPCRs-mediated signal transduction pathway. Recent research shows that GRKs also interact with non-GPCRs and participate in signal transduction in non-phosphorylated manner. Besides, GRKs activity can be regulated by multiple factors. Changes in GRKs expression have featured prominently in various tumor pathologies, and they are associated with angiogenesis, proliferation, migration, and invasion of malignant tumors. As a result, GRKs have been intensively studied as potential therapeutic targets. Herein, we review evolving understanding of the function of GRKs, the regulation of GRKs activity and the role of GRKs in human malignant tumor pathophysiology.
G 蛋白偶联受体激酶（GRKs）属于丝氨酸/苏氨酸蛋白激酶家族，能够特异地识别和磷酸化激动剂激活的 G 蛋白偶联受体（GPCRs），从而终止 GPCR 介导的信号转导通路。最近的研究表明，GRKs 还可以与非 GPCR 相互作用，并以非磷酸化的方式参与信号转导。此外，GRKs 的活性可以受到多种因素的调节。GRKs 表达的变化在各种肿瘤病理中表现明显，与恶性肿瘤的血管生成、增殖、迁移和侵袭有关。因此，GRKs 作为潜在的治疗靶点受到了广泛的研究。本文综述了 GRKs 的功能、GRKs 活性的调节以及在人类恶性肿瘤病理生理学中的作用的最新研究进展。
