School of Biosciences, University of Birmingham, Edgbaston, United Kingdom.
PLoS One. 2012;7(2):e31423. doi: 10.1371/journal.pone.0031423. Epub 2012 Feb 13.
ROCK1 and ROCK2 are serine/threonine kinases that function downstream of the small GTP-binding protein RhoA. Rho signalling via ROCK regulates a number of cellular functions including organisation of the actin cytoskeleton, cell adhesion and cell migration.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we use RNAi to specifically knockdown ROCK1 and ROCK2 and analyse their role in assembly of adhesion complexes in human epidermal keratinocytes. We observe that loss of ROCK1 inhibits signalling via focal adhesion kinase resulting in a failure of immature adhesion complexes to form mature stable focal adhesions. In contrast, loss of ROCK2 expression results in a significant reduction in adhesion complex turnover leading to formation of large, stable focal adhesions. Interestingly, loss of either ROCK1 or ROCK2 expression significantly impairs cell migration indicating both ROCK isoforms are required for normal keratinocyte migration.
ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes.
ROCK1 和 ROCK2 是丝氨酸/苏氨酸激酶，其在小分子 GTP 结合蛋白 RhoA 下游发挥作用。通过 ROCK 的 Rho 信号调节许多细胞功能，包括肌动蛋白细胞骨架的组织、细胞黏附和细胞迁移。
方法/主要发现：在这项研究中，我们使用 RNAi 特异性敲低 ROCK1 和 ROCK2，并分析它们在人表皮角质形成细胞中黏附复合物组装中的作用。我们观察到 ROCK1 的缺失抑制了粘着斑激酶的信号转导，导致不成熟的黏附复合物无法形成成熟稳定的粘着斑。相比之下，ROCK2 表达的缺失导致黏附复合物周转率显著降低，导致大而稳定的粘着斑形成。有趣的是，无论是 ROCK1 还是 ROCK2 的缺失都显著地损害了细胞迁移，这表明两种 ROCK 同工酶对正常角质形成细胞迁移都是必需的。
ROCK1 和 ROCK2 在人表皮角质形成细胞黏附复合物组装和周转率中具有不同且独立的作用。
