Rho-associated coiled-coil containing protein kinase (ROCK) (ROCK)

Rho-associated coiled-coil containing protein kinase (ROCK) is a serine/threonine kinase that serves as a primary downstream effector of the small GTPase RhoA (UniProt P70335, O75116). It exists in two highly homologous isoforms, ROCK1 and ROCK2, which are essential regulators of the actin cytoskeleton, controlling processes such as cell shape, motility, and smooth muscle contraction (PubMed: 25831510). ROCK functions by phosphorylating substrates like myosin light chain (MLC) and myosin phosphatase, thereby promoting actomyosin contractility (StatPearls: NBK554444). Overactivation of the ROCK pathway is linked to various conditions, including hypertension, glaucoma, and metastatic cancer progression (PubMed: 16551239). Therapeutic targeting of ROCK has led to the approval of several inhibitors; for instance, netarsudil is used to lower intraocular pressure in glaucoma, while belumosudil is approved for chronic graft-versus-host disease (FDA: NDA 208254, NDA 214783). These inhibitors generally function by blocking the ATP-binding pocket of the kinase, effectively dampening the signaling pathways that drive pathological cellular behaviors.

Other names

ROCK1ROCK2Rho-associated protein kinasep160ROCKROK-alphaROK-betaRho-associated kinase

Competitive inhibition of the ATP-binding site of ROCK1 and ROCK2, preventing the phosphorylation of downstream substrates such as myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1), which leads to reduced actomyosin contractility and cytoskeletal remodeling (PubMed: 21261665).