ROCK2

ROCK2, or Rho-associated coiled-coil containing protein kinase 2, is a serine/threonine kinase that belongs to the ROCK family, alongside ROCK1. In humans, ROCK2 is encoded by the ROCK2 gene. The protein is activated by binding of RhoA in its GTP-bound form to a regulatory region, which relieves autoinhibition by the C-terminal segment and enables phosphorylation of downstream substrates.

ROCK2 phosphorylates several targets that regulate the actin cytoskeleton. A principal pathway involves phosphorylation of myosin light chain (MLC) and of myosin phosphatase target subunit 1 (MYPT1), leading to increased MLC phosphorylation and enhanced contractility. ROCK2 also modulates actin dynamics indirectly by activating LIM kinase, which phosphorylates cofilin and promotes actin filament stabilization. Through these actions, ROCK2 influences cell shape, adhesion, migration, and cytokinesis, and it also affects smooth muscle contraction and vascular barrier function. In the nervous system, ROCK2 participates in neurite outgrowth and synaptic structure, contributing to neural development and plasticity.

Expression of ROCK2 is widespread, with notable presence in the brain, heart, kidney, and smooth muscle tissues. Its activity is important for normal development and tissue homeostasis, but dysregulated ROCK2 signaling has been linked to diseases such as cardiovascular disorders, fibrosis, pulmonary arterial hypertension, and cancer metastasis.

Pharmacological inhibition of ROCK enzymes is a common research strategy. Nonselective inhibitors, such as Y-27632 and fasudil, target both ROCK1 and ROCK2 and are used in laboratory studies and, in clinical contexts, for certain vascular conditions. Ripasudil (K-115) is approved in some regions for glaucoma and ocular hypertension. Confidence in selective ROCK2 inhibitors is increasing as a means to reduce side effects associated with broad ROCK inhibition.