ArticleNature communications2015
A molecular ruler regulates cytoskeletal remodelling by the Rho kinases.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- The ROCK1 PHC1 domain mediates recruitment to Rho activity zones and contractility signaling.Life science alliance · 2026Article
- GAK antagonises ROCK-dependent regulation of actomyosin dynamics.Journal of cell science · 2026Article
- A predictive mechanochemical modeling framework for the deformation and remodeling of the nuclear lamina.bioRxiv : the preprint server for biology · 2026Article
- Opposing effects of Rho-associated coiled-coil kinase 1 (ROCK1) and ROCK2 in TGF-β-SMAD signaling.Cell communication and signaling : CCS · 2026Article
- Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression.Cancer cell · 2025Article
- Illuminating understudied kinases: a generalizable biosensor development method applied to protein kinase N.Communications biology · 2025Article
- Rock inhibitors in Alzheimer's disease.Frontiers in aging · 2025Review
- 3D spheroids versus 2D-cultured human adipose stem cells to generate smooth muscle cells in an internal anal sphincter-targeting cryoinjured mouse model.Stem cell research & therapy · 2024Article
- Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024Review
- Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury.International journal of molecular sciences · 2024Review
- A critical evaluation of protein kinase regulation by activation loop autophosphorylation.eLife · 2023Article
- Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation.International journal of molecular sciences · 2023Article
- A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.Nature metabolism · 2023Article
- Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model.Journal of clinical medicine · 2023Article
- SCYL3, as a novel binding partner and regulator of ROCK2, promotes hepatocellular carcinoma progression.JHEP reports : innovation in hepatology · 2023Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- Engineered kinases as a tool for phosphorylation of selected targets in vivo.The Journal of cell biology · 2022Article
- SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK.Molecular oncology · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The Rho-associated coiled-coil kinases (ROCK) are essential regulators of the actin cytoskeleton; however, the structure of a full-length ROCK is unknown and the mechanisms by which its kinase activity is controlled are not well understood. Here we determine the low-resolution structure of human ROCK2 using electron microscopy, revealing it to be a constitutive dimer, 120 nm in length, with a long coiled-coil tether linking the kinase and membrane-binding domains. We find, in contrast to previous reports, that ROCK2 activity does not appear to be directly regulated by binding to membranes, RhoA, or by phosphorylation. Instead, we show that changing the length of the tether modulates ROCK2 function in cells, suggesting that it acts as a molecular ruler. We present a model in which ROCK activity is restricted to a discrete region of the actin cytoskeleton, governed by the length of its coiled-coil. This represents a new type of spatial control, and hence a new paradigm for kinase regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.