Department of Pharmacology, University of Washington School of Medicine, 1959 NE Pacific St., Box 357750, Seattle, WA 98195, U.S.A.
Department of Medicine (Hematology/Oncology), Quantitative Biosciences Institute, UCSF Helen Diller Family Cancer Center, 1700 4th St., San Francisco, CA 94143, U.S.A.
Biochem J. 2024 Nov 20;481(22):1659-1677. doi: 10.1042/BCJ20230352.
Protein kinase A (PKA) is a basophilic kinase implicated in the modulation of many cell-signaling and physiological processes. PKA also contributes to cancer-relevant events such as growth factor action, cell cycle control, cell migration and tumor metabolism. Germline and somatic mutations in PKA, gene amplifications, and chromosome rearrangements that encode kinase fusions, are linked to a growing number of malignant neoplasms. Mislocalization of PKA by exclusion from A-Kinase Anchoring Protein (AKAP) signaling islands further underlies cancer progression. This article highlights the influence of AKAP signaling and local kinase action in selected hallmarks of cancer. We also feature the utility of kinase inhibitor drugs as frontline and future anti-cancer therapies.
蛋白激酶 A(PKA)是一种碱性激酶,参与调节许多细胞信号和生理过程。PKA 还参与与癌症相关的事件,如生长因子作用、细胞周期控制、细胞迁移和肿瘤代谢。PKA 的种系和体细胞突变、基因扩增以及编码激酶融合的染色体重排与越来越多的恶性肿瘤有关。PKA 通过从 A-激酶锚定蛋白(AKAP)信号岛中排除而发生的定位错误进一步成为癌症进展的基础。本文重点介绍了 AKAP 信号和局部激酶活性在癌症的某些特征中的影响。我们还介绍了激酶抑制剂药物作为一线和未来抗癌治疗的应用。