Rho-associated protein kinase (ROCK) (ROCK)

Rho-associated protein kinase (ROCK) is a serine/threonine kinase belonging to the AGC family and serves as a primary downstream effector of the small GTPase RhoA [1, 6]. It exists in two highly homologous isoforms, ROCK1 and ROCK2, which are ubiquitously expressed but show tissue-specific enrichment in the lungs/liver and brain/heart, respectively [5, 6]. ROCK plays a fundamental role in regulating the actin cytoskeleton, cell motility, and smooth muscle contraction by phosphorylating substrates like myosin light chain and myosin phosphatase [3, 11]. Dysregulation of the Rho/ROCK pathway is a key driver in various pathologies, including cardiovascular diseases such as hypertension and vasospasm, as well as glaucoma and cancer metastasis [7, 14, 15]. Consequently, ROCK has become a significant therapeutic target; inhibitors like netarsudil and ripasudil are clinically used for glaucoma, while fasudil is employed for cerebral vasospasm [4, 13]. Beyond these applications, ROCK inhibitors are being investigated for their potential in treating neurodegenerative disorders, asthma, and fibrotic conditions [5, 12].

Other names

Rho-kinaseROKp160ROCKRho-associated coiled-coil containing protein kinase

Competitive inhibition of ATP binding to the kinase domain of ROCK1 and ROCK2, preventing the phosphorylation of downstream substrates such as myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1), which leads to cytoskeletal relaxation and reduced contractility [2, 12, 13].