Rock1

Olson, M. F. (2006) Rock1. AFCS-Nature Molecule Pages, (doi: 10.1038/mp.a002088.01)

Abstract

The major cellular function of ROCK1 is to regulate cell morphology, largely through the regulation of actin–myosin and intermediate filaments. As a result, ROCK1 directly influences several cellular activities, such as contraction, cytokinesis, adhesion, motility, endothelial barrier function, and membrane blebbing; it also indirectly influences processes such as gene transcription, proliferation, cell size, and survival. The wide range of processes influenced by ROCK1 means that it is involved in many physiological functions (such as neuronal morphogenesis, smooth muscle contraction, immune cell chemotaxis, and epithelial sheet movements) and in pathophysiological conditions (such as tumor cell metastasis, hypertension, vasospasm, bronchial asthma, and glaucoma). ROCK1 has a paralog in ROCK2, which has 65% identity overall with the highest degree of similarity in their kinase domains with 92% identity. Although prokaryotes have two ROCK paralogs, eukaryotes such as Drosophila melanogaster (DRok) and Caenorhabditis elegans (LET-502) have only a ROCK2 homolog, suggesting that it is the ancestral form. Interestingly, genetic evidence from these organisms indicates that these ancestral versions are involved in the regulation of actin cytoskeletal structures, cell morphology and motility. Much of the research that has been undertaken to identify ROCK substrates has made use of ROCK2; it has been generally assumed that the same proteins are also ROCK1 substrates. It has been determined that ROCK1, but not ROCK2, is negatively regulated by Rnd3/RhoE and Gem, and to be caspase-cleaved and activated during apoptosis. Functionally, ROCK1 might have a more significant function in regulating the actin–myosin cytoskeleton and phagocytosis, possibly as a result of differences in phosphatidylinositol lipid binding and subcellular localization. Data from the ROCK1 knockout mouse indicates that ROCK1 regulation of actin–myosin filaments is essential in closure of the eyelids and ventral body wall.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Olson, Professor Michael
• Authors: Olson, M. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: AFCS-Nature Molecule Pages
• Publisher: University of California, San Diego
• ISSN: 1477-5921
• ISSN (Online): 2328-8124
• Published Online: 13 January 2006