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Rho-associated protein kinase

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Human ROCK1 kinase domain complex with thiazole inhibitor (PDB code 4yve)

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1 Function
2 Disease
3 Relevance
4 Structural highlights
5 3D structures of Rho-associated protein kinase
6 References

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. ROCKs are kinases belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases.

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. making interactions with a ^[4].

3D structures of Rho-associated protein kinase

Rho-associated protein kinase 3D structures

References

↑ 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
↑ 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
↑ 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
↑ 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