ROCK2 gene

The ROCK2 gene (ROCK2 stands for: "Rho Associated Coiled-Coil Containing Protein Kinase 2") is a protein coding gene located on chromosome 2p25.1. The protein encoded by this gene is a serine/threonine kinase (Rho kinase) that regulates cytokinesis, smooth muscle contraction, actin stress fiber formation, and activation of the c-fos serum response element.

Rho kinases are activated by the GTPases produced by RhoA. They are modulators of processes involving cytoskeletal restructuring, such as focal adhesion formation, cell motility, and tumor cell invasion.

ROCK2 protein is involved in the regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber formation and focal adhesion, neurite retraction, cell adhesion, and motility through phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A, and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation.

Plays an important role in the timely initiation of centrosome duplication. Inhibits terminal differentiation of keratinocytes.

Diseases associated with ROCK2 include ureteral obstruction and breast cancer.

Since the discovery of the ROCK pathway more than 20 years ago, a growing body of research has unraveled the myriad effects of this pathway on tissue response to stress and injury. Dysregulated ROCK activity has been associated with a broad spectrum of diseases ranging from cardiovascular and neurological disorders to immune-mediated and fibrotic diseases. Although the two ROCK isoforms, ROCK1 and ROCK2, share >90% homology within their kinase domains, the function of these proteins is not redundant and depends on the cellular system in which they are expressed and activated (Zanin-Zhorov A et al. 2021).

1. Nalkurthi C et al (2021) ROCK2 inhibition attenuates profibrogenic immune cell function to reverse thioacetamide-induced liver fibrosis. JHEP Rep 4:100386.
2. Zanin-Zhorov A et al (2021) ROCK2, a critical regulator of immune modulation and fibrosis has emerged as a therapeutic target in chronic graft-versus-host disease. Clin Immunol 230:108823.