PURPOSE Adult salamander photoreceptors retract existing axons and extend new neuritic processes in vitro. In mammalian retina, similar forms of structural plasticity occur in injury and disease. The authors asked whether RhoA is present in photoreceptor axon terminals and whether activity in the RhoA-ROCK pathway contributes to the structural plasticity observed in rod and cone cells. METHOD...

PRK1 (PKN) is a serine/threonine kinase that has been shown to be activated by RhoA (Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Science 271, 648– 650). Detailed analysis of the PRK1 region involved in RhoA binding has revealed that two homologous sequences within the HR1 domain (HR1a and HR1b) both bind to RhoA; the thi...

RhoA, a member of the Rho family small GTPases, has been shown to play important roles in axon guidance. However, to date, the physiological function of RhoA in axon guidance events in vivo has not been determined genetically in animals. Here we show that RhoA mRNA is strongly expressed by sensory neurons in the developing mouse dorsal root ganglia (DRG). We have deleted RhoA in sensory neurons...

Cytotoxic necrotizing factor types 1 and 2 (CNF1 and -2) produced by pathogenic Escherichia coli strains have 90% conserved residues over 1,014-amino-acid sequences. Both CNFs are able to provoke a remarkable increase in F-actin structures in cultured cells and covalently modify the RhoA small GTPases. In this study, we demonstrated that CNF2 reduced RhoA GTPase activity in the presence and abs...

The intestinal epithelial barrier, which is regulated by the actin cytoskeleton, exhibits permeability changes during inflammation. Here we show that activation of the CysLT(1) receptor by the inflammatory mediator leukotriene D(4) (LTD(4)) causes a rapid increase in stress-fibre formation in intestinal epithelial cells. This effect was mimicked by cytotoxic necrotising factor-1 (CNF-1)-induced...

Peng F, Zhang B, Wu D, Ingram AJ, Gao B, Krepinsky JC. TGF -induced RhoA activation and fibronectin production in mesangial cells require caveolae. Am J Physiol Renal Physiol 295: F153–F164, 2008. First published April 23, 2008; doi:10.1152/ajprenal.00419.2007.—Glomerular sclerosis of diverse etiologies is characterized by mesangial matrix accumulation, with transforming growth factor(TGF ) an ...

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide s...

The aim of the present study was to observe the influence of various factors on the nuclear distribution of the RhoA protein in the SGC-7901 human gastric cancer cell line. Immunofluorescence microscopy was used to detect the localization of the RhoA protein, and Western blotting was used to determine the quantity of RhoA in the nucleus, cytosol and membrane. The results showed that H2O2-mediat...

p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways. We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility. RSK1 activation and p27pT198 both increase in early G(1). As for many kinase-substrate pairs, cellular RSK1 coprecipitates with p27. siRNA to RSK1 and RSK1 inhibition both rapidly reduce cellul...

Transendothelial migration of monocytes is the process by which monocytes leave the circulatory system and extravasate through the endothelial lining of the blood vessel wall and enter the underlying tissue. Transmigration requires coordination of alterations in cell shape and adhesive properties that are mediated by cytoskeletal dynamics. We have analyzed the function of RhoA in the cytoskelet...