Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , 84 West Huai-hai Road, Xuzhou, Jiangsu , China +86 0516 85582513 ;
Expert Opin Ther Targets. 2014 Jul;18(7):807-15. doi: 10.1517/14728222.2014.918103. Epub 2014 May 29.
Overexpression of p21-activated kinase 5 (PAK5) is discovered in many tumors, probably due to its regulation in cytoskeleton, antiapoptosis and proliferation. A better understanding of the modulation mechanisms of PAK5 is needed for the development of tumor treatment where current therapeutics is inadequate.
This review discusses the current understanding of PAK5 functions as an oncogenic kinase in tumor cellular regulation. Mechanisms of action and molecular pathways involved in cytoskeleton regulation, antiapoptosis and proliferation of tumors are discussed.
PAKs are serine/threonine kinases and downstream effectors for Cdc42 and Rac, the subfamilies of Rho small GTPases. PAK5 shares sequence identities in p21-GTPase-binding domain and kinase domain and is completely different in other regions compared with other PAKs. Overexpression of PAK5 has been found in several tumors, probably due to its contribution to proliferation, cytoskeleton and anti-apoptosis. Additional regulation mechanisms which are independent of Rho GTPases also indicate that PAK5 functions as a special signal molecule in cellular signaling pathways of tumor progression.
许多肿瘤中发现 p21 激活激酶 5（PAK5）表达过度，这可能与其在细胞骨架、抗凋亡和增殖中的调节有关。为了开发当前治疗方法不足的肿瘤治疗方法，需要更好地了解 PAK5 的调节机制。
本综述讨论了 PAK5 作为致癌激酶在肿瘤细胞调节中的作用的现有理解。讨论了参与细胞骨架调节、肿瘤抗凋亡和增殖的作用机制和分子途径。
PAKs 是丝氨酸/苏氨酸激酶，是 Cdc42 和 Rac 的下游效应物，Cdc42 和 Rac 是 Rho 小 GTP 酶的亚家族。PAK5 在 p21-GTP 结合域和激酶域与其他 PAKs 具有序列同一性，而在其他区域则完全不同。PAK5 的过表达已在几种肿瘤中发现，这可能是由于其对增殖、细胞骨架和抗凋亡的贡献。独立于 Rho GTPases 的其他调节机制也表明 PAK5 作为肿瘤进展细胞信号通路中的特殊信号分子发挥作用。
