Rho-associated coiled-coil containing protein kinase 2 (ROCK2) (ROCK2)

Rho-associated coiled-coil containing protein kinase 2 (ROCK2) is a serine/threonine kinase and key effector of the small GTPase RhoA, primarily regulating actin cytoskeleton dynamics, cell polarity, and contractility through phosphorylation of substrates like myosin light chain (MLC), LIM kinase, and cofilin. It promotes stress fiber formation, focal adhesions, smooth muscle contraction, and cytokinesis while also influencing neurite retraction, cell adhesion, and autophagy. ROCK2 is highly expressed in brain, heart, and spinal cord, with subcellular localization at stress fibers, centrosomes, and the cleavage furrow. In disease, ROCK2 hyperactivity contributes to neurodegeneration in Alzheimer's via impaired dendritic spine stability and tau accumulation, cancer progression through enhanced invasion, inflammation via macrophage polarization, and cardiovascular issues like hypertension. Pharmacological inhibition by drugs like Fasudil (pan-ROCK) or selective agents like SR3677 reduces pathological contractility, promotes autophagic clearance of amyloid-beta and tau, and shows promise in models of Alzheimer's, glaucoma, and autoimmunity, though challenges include managing cytoskeletal side effects.

Other names

Rho-associated protein kinase 2ROCK-II

Inhibition of kinase activity leading to reduced actomyosin contractility, Decreased phosphorylation of myosin light chain (MLC) and LIM kinase, Promotion of autophagy and lysosomal degradation, Reduction of actin stress fibers and focal adhesions