Rho-associated protein kinase

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spinqualitylabelsall models Human ROCK1 kinase domain complex with thiazole inhibitor (PDB code 4yve) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Rho-associated protein kinase (ROCK) is a Rho GTPase effector. ROCK has been shown to regulate cadherin function and thus cell-cell adhesion[1]. ROCKs phosphorylate a large number of actin-binding proteins to modulate their functions. Disease Aberrant ROCK expression and activation contribute to cancer development. ROCK levels are elevated in testicular, bladder and esophageal cancers[2]. Relevance ROCK inhibitors have potential to be developed for treatment of glaucoma and other ocular diseases[3]. Structural highlights ROCK contains several domains including (in ROCK1) a kinase domain (residues 76-338); a coiled-coil region (residues 339-1103) which contains a Rho-binding domain (residues 934-1015) and a pleckstrin homology and cysteine-rich domain (residues 1103-1320) at the C-terminal. ROCK1 inhibitor binds in a pocket making interactions with a glycine-rich loop[4].

3D structures of Rho-associated protein kinase

Updated on 06-March-2017

References

1. ↑ Smith AL, Dohn MR, Brown MV, Reynolds AB. Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin. Mol Biol Cell. 2012 Jan;23(1):99-110. doi: 10.1091/mbc.E11-06-0497. Epub 2011 Oct, 26. PMID:22031287 doi:http://dx.doi.org/10.1091/mbc.E11-06-0497
2. ↑ Schofield AV, Bernard O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol. 2013 Jul-Aug;48(4):301-16. doi:, 10.3109/10409238.2013.786671. Epub 2013 Apr 19. PMID:23601011 doi:http://dx.doi.org/10.3109/10409238.2013.786671
3. ↑ Honjo M, Tanihara H, Inatani M, Kido N, Sawamura T, Yue BY, Narumiya S, Honda Y. Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Invest Ophthalmol Vis Sci. 2001 Jan;42(1):137-44. PMID:11133858
4. ↑ Green J, Cao J, Bandarage UK, Gao H, Court J, Marhefka C, Jacobs M, Taslimi P, Newsome D, Nakayama T, Shah S, Rodems S. Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors. J Med Chem. 2015 Jun 12. PMID:26039570 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00424