Rho-associated protein kinase

Not to be confused with Rho Chi.
ROCK
Crystal structure of human ROCK I
Identifiers
SymbolRho-associated protein kinase
Alt. symbolsRho-associated, coiled-coil-containing protein kinase
NCBI gene579202
Other data
EC number2.7.11.1

Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton.

ROCKs (ROCK1 and ROCK2) occur in mammals (human, rat, mouse, cow), zebrafish, Xenopus, invertebrates (C. elegans, mosquito, Drosophila) and chicken. Human ROCK1 has a molecular mass of 158 kDa and is a major downstream effector of the small GTPase RhoA. Mammalian ROCK consists of a kinase domain, a coiled-coil region and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by an autoinhibitory intramolecular fold if RhoA-GTP is not present.[1][2]

Rat ROCKs were discovered as the first effectors of Rho and they induce the formation of stress fibers and focal adhesions by phosphorylating MLC (myosin light chain).[3] Due to this phosphorylation, the actin binding of myosin II and, thus, the contractility increases. Two mouse ROCK isoforms ROCK1 and ROCK2 have been identified. ROCK1 is mainly expressed in the lung, liver, spleen, kidney and testis. However, ROCK2 is distributed mostly in the brain and heart.[1][2][4]

Protein kinase C and Rho-associated protein kinase are involved in regulating calcium ion intake; these calcium ions, in turn stimulate a myosin light chain kinase, forcing a contraction.[5] Rho-associated protein kinase are serine or threonine kinases that determine the calcium sensitivity in smooth muscle cells.

  1. ^ a b Hahmann C, Schroeter T (January 2010). "Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity". Cellular and Molecular Life Sciences. 67 (2): 171–7. doi:10.1007/s00018-009-0189-x. PMC 11115778. PMID 19907920. S2CID 6445354.
  2. ^ a b Riento K, Ridley AJ (June 2003). "Rocks: multifunctional kinases in cell behaviour". Nature Reviews. Molecular Cell Biology. 4 (6): 446–56. doi:10.1038/nrm1128. PMID 12778124. S2CID 40665081.
  3. ^ Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton". Molecular and Cellular Biology. 16 (10): 5313–27. doi:10.1128/mcb.16.10.5313. PMC 231530. PMID 8816443.
  4. ^ Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S (August 1996). "ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice". FEBS Letters. 392 (2): 189–93. doi:10.1016/0014-5793(96)00811-3. PMID 8772201. S2CID 6684411.
  5. ^ Anjum I (June 2018). "Calcium sensitization mechanisms in detrusor smooth muscles". Journal of Basic and Clinical Physiology and Pharmacology. 29 (3): 227–235. doi:10.1515/jbcpp-2017-0071. PMID 29306925. S2CID 20486807.