Rho-associated protein kinase 1 (ROCK1) and Rho-associated protein kinase 2 (ROCK2) (ROCK1, ROCK2)

Rho-associated protein kinase 1 (ROCK1) and Rho-associated protein kinase 2 (ROCK2) are serine/threonine kinases that function as downstream effectors of the small GTPase RhoA, as part of the AGC kinase family (PKA/PKG/PKC-related kinases)[1][5]. They are central regulators of the actin cytoskeleton, controlling cellular processes such as shape, motility, contraction, division, and polarity through phosphorylation of various downstream targets including myosin light chain and LIM kinase[1][5][7]. ROCK1 and ROCK2 share significant structural homology but have some tissue-specific expression patterns and regulatory differences; ROCK1 is prevalent in lung and immune cells, while ROCK2 is prominent in the brain and heart[5]. Their dysregulation is implicated in a wide range of pathologies, including cancer, cardiovascular, neurodegenerative, and fibrotic diseases. Several small-molecule ROCK inhibitors are in clinical use or development for conditions such as cerebral vasospasm, glaucoma, fibrotic disorders, and cancer[5].

Other names

Rho-associated coiled-coil containing protein kinase 1Rho-associated coiled-coil containing protein kinase 2Rho-kinase alpha (ROKα / ROKA) (for ROCK1)Rho-kinase beta (ROKβ / ROKB) (for ROCK2)Rho-associated kinase 1/2

Inhibition of serine/threonine kinase activity - Interference with Rho/ROCK-mediated phosphorylation of myosin light chain (MLC) - Modulation of actin-myosin contractility - Suppression of cell migration, proliferation, and fibrosis