Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, and Cancer Biology Program, The Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio.
Department of Hematology and Medical Oncology, Emory University and Winship Cancer Institute, Atlanta, Georgia.
Endocrinology. 2020 Aug 1;161(8). doi: 10.1210/endocr/bqaa105.
The family of p21-activated kinases (PAKs) are oncogenic proteins that regulate critical cellular functions. PAKs play central signaling roles in the integrin/CDC42/Rho, ERK/MAPK, PI3K/AKT, NF-κB, and Wnt/β-catenin pathways, functioning both as kinases and scaffolds to regulate cell motility, mitosis and proliferation, cytoskeletal rearrangement, and other cellular activities. PAKs have been implicated in both the development and progression of a wide range of cancers, including breast cancer, pancreatic melanoma, thyroid cancer, and others. Here we will discuss the current knowledge on the structure and biological functions of both group I and group II PAKs, as well as the roles that PAKs play in oncogenesis and progression, with a focus on thyroid cancer and emerging data regarding BRAF/PAK signaling.
p21 激活激酶(PAKs)家族是致癌蛋白,调节关键的细胞功能。PAKs 在整合素/CDC42/Rho、ERK/MAPK、PI3K/AKT、NF-κB 和 Wnt/β-catenin 通路中发挥核心信号作用,既是激酶又是支架,调节细胞迁移、有丝分裂和增殖、细胞骨架重排和其他细胞活动。PAKs 参与了广泛的癌症的发展和进展,包括乳腺癌、胰腺黑色素瘤、甲状腺癌等。在这里,我们将讨论关于 I 组和 II 组 PAKs 的结构和生物学功能的最新知识,以及 PAKs 在致癌和进展中的作用,重点关注甲状腺癌和关于 BRAF/PAK 信号的新兴数据。