Rho-associated coiled-coil kinase (ROCK)

Rho-associated coiled-coil kinase (ROCK) is a serine/threonine kinase in the AGC family, acting as a key downstream effector of RhoA GTPase to regulate actin cytoskeleton dynamics, cell shape, migration, and contractility. It promotes stress fiber formation and focal adhesions by phosphorylating myosin light chain (MLC) directly or inactivating MLC phosphatase, and by activating LIM kinase to inhibit cofilin-mediated actin depolymerization. ROCK also contributes to cytokinesis, cell polarity, and smooth muscle contraction, with autoinhibition relieved by Rho-GTP binding. In disease, elevated ROCK activity drives cancer progression, including neuroblastoma invasion and poor survival via high ROCK2 expression, as well as angiogenesis in tumors and vascular disorders. ROCK inhibitors like fasudil and Y-27632 suppress tumor growth, induce differentiation, and reduce metastasis in preclinical models by blocking these pathways, positioning ROCK as a promising therapeutic target despite challenges in isoform specificity.

Other names

Rho-associated protein kinaseRho-kinasep160ROCKROK

Inhibition of ROCK kinase activity leading to reduced actomyosin contractility, suppression of cell migration and invasion, induction of cell differentiation via GSK3β-mediated MYCN degradation, disruption of actin cytoskeleton stabilization