Information on EC 2.7.11.39 - ROCK-subfamily protein kinase

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 , and myosin regulatory light chain (MRLC2/MYL12B) that regulates Myosin II. In Drosophila it is involved 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 . It is activated by Rho1, the single homolog of human RhoA/B/C, which also activate ROCK.