Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components

Abstract

The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour.

Keywords: ROCK, Rho-associated coiled-coil forming kinase; Rho-kinase; cytoskeleton.

Figure 1

Molecular structure of ROCK 1 and ROCK 2. They are similar and both contain a kinase domain, coiled-coil region, rho-binding domain, putative pleckstrin homology domain (PHD) and cysteine-rich domain (CRD). Rho GEF = Rho guanine nucleotide exchange factor. Created with BioRender.com.

Figure 2

The functions of ROCK. Rho is activated by Rho guanine nucleotide exchange factor (GEF). Activated GTP-bound Rho stimulates ROCK. Activated ROCK activates or inhibits downstream targets by phosphorylation. Activated ROCK regulates microfilaments via the ROCK/MYPT1/MLC and ROCK/LIM kinases/cofilin pathways. ROCK also regulates intermediate filaments by phosphorylation. ROCK regulates microtubules by phosphorylation of several microtubule-associated proteins such as MAP2/Tau, collapsin response mediator protein 2 (CRMP2) and Doublecortin. Created with BioRender.com.