Rhoassociated

Rho-associated, coiled-coil containing protein kinase, usually abbreviated ROCK, refers to two closely related serine/threonine kinases, ROCK1 and ROCK2. They are key downstream effectors of the small GTPase RhoA and are activated when RhoA binds to a regulatory region in the kinases. Both isoforms share a common architecture that includes an N-terminal kinase domain and a C-terminal regulatory region involved in autoinhibition and Rho-binding.

ROCK proteins regulate the actin cytoskeleton and cellular contractility. They phosphorylate targets such as myosin light chain (MLC) and the myosin light chain phosphatase regulatory subunit MYPT1, promoting actin-myosin contraction, stress fiber formation, and focal adhesions. These actions influence cell shape, motility, adhesion, and barrier function in various tissues. ROCK also affects smooth muscle contraction and participates in neuronal growth cone dynamics and axon outgrowth.

Regulation of ROCK activity is primarily controlled by RhoA-GTP binding, which relieves autoinhibition, allowing kinase activity. In addition to this canonical activation, ROCK can be modulated by other signaling events and proteolytic processing. Several small-molecule inhibitors, notably fasudil and Y-27632, are widely used in research and have been explored for therapeutic applications in conditions such as vasospasm, pulmonary hypertension, fibrosis, and cancer metastasis. Inhibition of ROCK can reduce stress fibers and focal adhesions, altering cell migration and vascular tone.

ROCK signaling is conserved across vertebrates and plays a broad role in cytoskeletal regulation and tissue remodeling. Ongoing research aims to clarify isoform-specific functions and develop selective inhibitors with favorable safety profiles.

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