Rho kinase

Rho-associated protein kinase
File:Rho kinase structure.png Crystal structure of Rho kinase
Identifiers
EC number	2.7.11.1
CAS number	138559-60-5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

Rho kinase (ROCK) is a serine/threonine-specific protein kinase that is involved in regulating the shape and movement of cells by acting on the cytoskeleton. It is a downstream effector of the small GTPase RhoA, which is part of the Rho family of GTPases. Rho kinase plays a crucial role in various cellular functions, including contraction, motility, proliferation, and apoptosis.

Structure

Rho kinase is composed of several domains, including a kinase domain, a coiled-coil domain, and a pleckstrin homology (PH) domain. The kinase domain is responsible for its enzymatic activity, while the coiled-coil domain mediates dimerization and interaction with other proteins. The PH domain is involved in membrane association and regulation of the kinase activity.

Isoforms

There are two isoforms of Rho kinase: ROCK1 and ROCK2. These isoforms are encoded by separate genes and have distinct tissue distributions and functions. ROCK1 is predominantly expressed in non-neuronal tissues, while ROCK2 is more abundant in the brain and heart.

Function

Rho kinase is involved in the regulation of the actin cytoskeleton, which is crucial for maintaining cell shape, polarity, and motility. It phosphorylates various substrates, including myosin light chain (MLC), LIM kinase, and adducin, leading to changes in actin filament dynamics and cell contractility.

Role in Disease

Rho kinase has been implicated in several diseases, including cardiovascular diseases, cancer, and neurological disorders. Inhibition of Rho kinase has been shown to have therapeutic potential in conditions such as hypertension, pulmonary arterial hypertension, and glaucoma.

Inhibitors

Several Rho kinase inhibitors have been developed, including fasudil and Y-27632. These inhibitors are used in research and have potential therapeutic applications in treating diseases associated with excessive Rho kinase activity.

Research and Clinical Implications

Rho kinase is a target for drug development due to its involvement in various pathological processes. Ongoing research aims to develop more selective and potent inhibitors to treat diseases such as cancer, fibrosis, and neurodegenerative disorders.

Also see

• RhoA
• Cytoskeleton
• Protein kinase
• Signal transduction