title: Made to measure - keeping Rho kinase at a distance.
abstract: The Rho-associated coiled-coil containing kinases (ROCK) were first identified as effectors of the small GTPase RhoA, hence their nomenclature. Since their discovery, two decades ago, scientists have sought to unravel the structure, regulation, and function of these essential kinases. During that time, a consensus model has formed, in which ROCK activity is regulated via both Rho-dependent and independent mechanisms. However, recent findings have raised significant questions regarding this model. In their recent publication in Nature Communications, Truebestein and colleagues present the structure of a full-length Rho kinase for the first time. In contrast to previous reports, the authors could find no evidence for autoinhibition, RhoA binding, or regulation of kinase activity by phosphorylation. Instead, they propose that ROCK functions as a molecular ruler, in which the central coiled-coil bridges the membrane-binding regulatory domains to the kinase domains at a fixed distance from the plasma membrane. Here, we explore the consequences of the new findings, re-examine old data in the context of this model, and emphasize outstanding questions in the field.
authors.affiliation: a Department of Structural and Computational Biology , Max F. Perutz Laboratories (MFPL), Vienna Biocenter (VBC) , Vienna , Austria.
authors.forename: Linda
authors.initials: L
authors.lastname: Truebestein
authors.affiliation: a Department of Structural and Computational Biology , Max F. Perutz Laboratories (MFPL), Vienna Biocenter (VBC) , Vienna , Austria.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Elsner
authors.affiliation: a Department of Structural and Computational Biology , Max F. Perutz Laboratories (MFPL), Vienna Biocenter (VBC) , Vienna , Austria.|b Department of Medical Biochemistry , Medical University of Vienna , Vienna , Austria.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Leonard
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D010766:Phosphorylation; D021381:Protein Transport; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases
keywords: GTPase; ROCK; RhoA; coiled-coil; cytoskeleton; kinase; membrane anchor; molecular ruler; stress fibers