Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
The enzyme has wide range known substrates, mostly involved in cytoskeletal regulation, with a preference for positive charges at P1 to P5.
Other name(s): ROCK; Rho Kinase; ROCK1; ROCK2; rok; let-402; ROCK-I (gene name); ROCK-II (gene name)
Systematic name: ATP:cytoskeleton-protein phosphotransferase
Comments: Requires Mg2+. An animal specific kinase that is duplicated in vertebrates (ROCK1, ROCK2), and with homologs in Drosophila (rok) and Caenorhabditis elegans (let-502). They are ~1300 amino-acid proteins, with an N-terminal kinase domain, with the AGC-specific kinase domain tail, followed by a central coiled-coil region, HR1 domain, Rho-binding domain (RBD), and PH domain. The PH domain is split by an inserted CRD (cysteine-rich Zn finger motif). ROCK is activated by the small GTPase Rho and modulates the cytoskeleton by phosphorylation of a wide array of other cytoskeletal proteins. Binding of Rho-GTP to the RBD relieves an intramolecular inhibition and activates the kinase activity. These kinases modulate the cytoskeleton in response to Rho GTPase signalling. Substrates include LIM-kinase (LIMK) which phosphorylates and inhibits cofilin, blocking its actin-depolymerizing function [1], and myosin regulatory light chain (MRLC2/MYL12B) in that regulates Myosin II. In Drosophila is involve in the planar cell polarity pathway, where it is genetically downstream of frizzled and dishevelled gene families, and phosphorylates the non-muscle myosin light chain, regulating Myosin II [2]. It is activated by Rho1, the single homolog of human RhoA/B/C, which also activate ROCK.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Ohashi, K., Nagata, K., Maekawa, M., Ishizaki, T., Narumiya, S. and Mizuno, K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J. Biol. Chem. 275 (2000) 3577-3582. [PMID: 10652353]
2. Winter, C.G., Wang, B., Ballew, A., Royou, A., Karess, R., Axelrod, J.D. and Luo, L. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 105 (2001) 81-91. [PMID: 11301004]