Rho-associated protein kinase 1 (ROCK1) (ROCK1)

The Rho-associated protein kinase 1 (ROCK1) is a key serine/threonine kinase and a major downstream effector of the small GTPase RhoA, forming the core of the RhoA/ROCK1 signaling pathway [1, 5]. This pathway is a master regulator of the actin cytoskeleton, governing essential cellular processes such as actomyosin contractility, cell migration, adhesion, and morphology [5, 7]. Upon activation by RhoA, ROCK1 phosphorylates substrates like myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1), leading to increased cellular tension and stress fiber formation [1, 8]. Dysregulation of RhoA/ROCK1 signaling is a hallmark of various pathologies, including cardiovascular diseases like hypertension and vasospasm, as well as glaucoma and metastatic cancer [1, 7, 10]. In the central nervous system, the pathway is often upregulated following injury, where it inhibits neurite outgrowth and axonal regeneration [3, 11]. Pharmacological inhibition of ROCK1, using drugs like fasudil and netarsudil, has proven clinically effective for treating cerebral vasospasm and reducing intraocular pressure [2, 4]. Ongoing research also explores the potential of ROCK inhibitors in treating fibrosis and neurodegenerative conditions [5, 7].

Other names

RhoA/ROCK1 pathwayp160ROCKROK betaRho-associated, coiled-coil containing protein kinase 1RhoA/ROCK signaling pathway

Inhibition of ROCK kinase activity, preventing the phosphorylation of downstream substrates such as myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1), which leads to reduced actomyosin contractility and stabilization of the actin cytoskeleton.