ROCK1

ROCK1, or Rho-associated coiled-coil containing protein kinase 1, is a serine/threonine kinase that functions as a downstream effector of the small GTPase RhoA. It is one of two ROCK family kinases, the other being ROCK2. The ROCK1 gene encodes this kinase in humans.

ROCK1 contains an N-terminal catalytic kinase domain, followed by a coiled-coil region and a C-terminal regulatory segment that maintains autoinhibition; binding of RhoA–GTP relieves this inhibition and activates kinase activity.

In cells, ROCK1 phosphorylates substrates including the myosin light chain (directly or via inhibition of the myosin phosphatase regulatory subunit MYPT1), LIM kinase, and others. This promotes actomyosin contractility, stress fiber formation, focal adhesion maturation, and changes in cell shape. ROCK1 also contributes to cytokinesis, cell migration, and neurite outgrowth, reflecting its central role in cytoskeletal dynamics.

Physiologically, ROCK1 influences vascular tone, smooth muscle contraction, and wound healing. Pathologically, dysregulation of ROCK1 has been linked to hypertension, pulmonary arterial hypertension, fibrosis, cancer cell invasion and metastasis, and glaucoma.

Because of its role in cytoskeletal regulation, ROCK1 is a target for pharmacological inhibition. Inhibitors such as fasudil and Y-27632 are widely used in research; ripasudil is approved in several countries for glaucoma. Inhibition can reduce contractility and migration, but may have side effects such as hypotension. Ongoing research seeks isoform-specific inhibitors and therapeutic applications.