Mali Raghuveer Singh, Kapur Simryn, Kapur Reuben
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Department of Pediatrics, Indianapolis, Indiana, USA.
Curr Opin Hematol. 2014 Jul;21(4):271-5. doi: 10.1097/MOH.0000000000000056.
Rho kinases (ROCKs) are involved in regulating a variety of physiologic functions including cytoskeletal reorganization, migration, adhesion, survival and proliferation. They do so via activating several different downstream substrates such as myosin light chain phosphatase, LIM kinase and ezrin/radixin/moesin proteins. To date, most of the conclusions with regard to the function of ROCKs have involved the use of cell line models, pharmacologic inhibitors and dominant negative approaches. Importantly, the role of ROCK in hematopoiesis or leukemogenesis in the context of whole organism remains poorly understood.
Recent studies utilizing mice deficient in the expression of ROCK1 have begun to shed some light into the physiologic role(s) of ROCK in both normal and abnormal hematopoiesis. Findings, thus far, suggest that ROCK plays an essential role in regulating growth and survival in different hematopoietic lineages via distinct mechanisms, in part, by utilizing distinct downstream substrates including maintaining the activation of tumor-suppressor genes.
In blood cells, emerging data suggest that ROCK plays an essential role in negatively regulating inflammatory and erythropoietic stress and positively regulates the growth and survival of leukemic cells.
Rho激酶（ROCKs）参与调节多种生理功能，包括细胞骨架重组、迁移、黏附、存活和增殖。它们通过激活几种不同的下游底物来实现这些功能，如肌球蛋白轻链磷酸酶、LIM激酶和埃兹蛋白/根蛋白/膜突蛋白。迄今为止，关于ROCKs功能的大多数结论都涉及细胞系模型、药理学抑制剂和显性阴性方法的使用。重要的是，在整个生物体的背景下，ROCK在造血或白血病发生中的作用仍知之甚少。
最近利用缺乏ROCK1表达的小鼠进行的研究，开始揭示ROCK在正常和异常造血中的生理作用。迄今为止的研究结果表明，ROCK通过不同机制在调节不同造血谱系的生长和存活中发挥重要作用，部分是通过利用不同的下游底物，包括维持肿瘤抑制基因的激活。
在血细胞中，新出现的数据表明，ROCK在负向调节炎症和红细胞生成应激中起重要作用，并正向调节白血病细胞的生长和存活。
