Zhao Zhou-shen, Manser Ed
GSK-IMCB Laboratory, Institute of Molecular and Cell Biology, Proteos Building, 61 Biopolis Drive, Singapore 138673.
Biochem J. 2005 Mar 1;386(Pt 2):201-14. doi: 10.1042/BJ20041638.
The Rho GTPases are a family of molecular switches that are critical regulators of signal transduction pathways in eukaryotic cells. They are known principally for their role in regulating the cytoskeleton, and do so by recruiting a variety of downstream effector proteins. Kinases form an important class of Rho effector, and part of the biological complexity brought about by switching on a single GTPase results from downstream phosphorylation cascades. Here we focus on our current understanding of the way in which different Rho-associated serine/threonine kinases, denoted PAK (p21-activated kinase), MLK (mixed-lineage kinase), ROK (Rho-kinase), MRCK (myotonin-related Cdc42-binding kinase), CRIK (citron kinase) and PKN (protein kinase novel), interact with and are regulated by their partner GTPases. All of these kinases have in common an ability to dimerize, and in most cases interact with a variety of other proteins that are important for their function. A diversity of known structures underpin the Rho GTPase-kinase interaction, but only in the case of PAK do we have a good molecular understanding of kinase regulation. The ability of Rho GTPases to co-ordinate spatial and temporal phosphorylation events explains in part their prominent role in eukaryotic cell biology.
Rho GTP酶是一类分子开关，是真核细胞信号转导途径的关键调节因子。它们主要因其在调节细胞骨架中的作用而闻名，通过招募多种下游效应蛋白来实现这一作用。激酶是Rho效应蛋白的重要类别，开启单个GTP酶所带来的部分生物学复杂性源于下游磷酸化级联反应。在这里，我们重点关注目前对不同的Rho相关丝氨酸/苏氨酸激酶（分别称为PAK（p21激活激酶）、MLK（混合谱系激酶）、ROK（Rho激酶）、MRCK（肌强直相关Cdc42结合激酶）、CRIK（瓜氨酸激酶）和PKN（新型蛋白激酶））与它们的伴侣GTP酶相互作用及受其调节方式的理解。所有这些激酶都具有二聚化能力，并且在大多数情况下与多种对其功能重要的其他蛋白质相互作用。多种已知结构支撑着Rho GTP酶 - 激酶相互作用，但只有在PAK的情况下，我们对激酶调节有很好的分子层面理解。Rho GTP酶协调空间和时间磷酸化事件的能力部分解释了它们在真核细胞生物学中的突出作用。
