Department of Biochemistry, Chungbuk National University College of Medicine, Cheongju, 28644, Korea.
Exp Mol Med. 2019 Feb 12;51(2):1-9. doi: 10.1038/s12276-018-0204-0.
p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival. Dysregulation of its expression and activity thus contributes to the development of diverse pathological conditions. PAK4 plays a pivotal role in cancer progression by accelerating the epithelial-mesenchymal transition, invasion, and metastasis. Therefore, PAK4 is regarded as an attractive therapeutic target in diverse types of cancers, prompting the development of PAK4-specific inhibitors as anticancer drugs; however, these drugs have not yet been successful. PAK4 is essential for embryonic brain development and has a neuroprotective function. A long list of PAK4 effectors has been reported. Recently, the transcription factor CREB has emerged as a novel effector of PAK4. This finding has broad implications for the role of PAK4 in health and disease because CREB-mediated transcriptional reprogramming involves a wide range of genes. In this article, we review the PAK4 signaling pathways involved in prostate cancer, Parkinson's disease, and melanogenesis, focusing in particular on the PAK4-CREB axis.
p21-激活的激酶 4（PAK4）是 PAK 家族的一员，调节广泛的细胞功能，包括细胞黏附、迁移、增殖和存活。其表达和活性的失调因此有助于多种病理状况的发展。PAK4 通过加速上皮-间充质转化、侵袭和转移，在癌症进展中发挥关键作用。因此，PAK4 被视为多种类型癌症中具有吸引力的治疗靶点，促使开发 PAK4 特异性抑制剂作为抗癌药物；然而，这些药物尚未成功。PAK4 对胚胎大脑发育至关重要，具有神经保护功能。已经报道了大量的 PAK4 效应物。最近，转录因子 CREB 已成为 PAK4 的一种新效应物。这一发现对 PAK4 在健康和疾病中的作用具有广泛的意义，因为 CREB 介导的转录重编程涉及广泛的基因。在本文中，我们综述了参与前列腺癌、帕金森病和黑色素生成的 PAK4 信号通路，特别关注 PAK4-CREB 轴。
