New angle of view on the role of rho/rho kinase pathway in human diseases.

Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca2+ sensitization through inactivation of myosin phosphatase. The major physiological functions of Rho/Rho-kinase cascade include contraction, proliferation and migration in cells.There are some excellent reviews about Rho/Rho-kinase signal pathway, most of which focus on the specific proteins of the pathway including some upstream regulators and its final effects. But few articles cover signal pathways that can activate the signaling concerned, and/or the pathways that Rho/Rho-kinase can exactly activate. This review hence highlights the two questions after a profound survey of published literatures. Rho/Rho-kinase can exert positive feedback with just another kinase/signal transducers and activator of transcription, receptor tyrosine kinase signal pathways, even reactive oxygen species, which seem to comprise certain signal loops. The authors also presume, accordingly, that the positive feedback suggests a possible reason for exacerbation of some kind of inflammatory diseases including asthma, rheumatoid arthritis, multiple sclerosis, atherosclerosis, etc. This essay, therefore, provides a new angle of view for the therapy of these kinds of diseases.