Sophisticated strategies have emerged to regulate the critical vegetative / parasitic transition in all pathogens, and in many cases, this regulation is provided by two-component regulatory systems. The VirA/VirG system of the plant pathogen Agrobacterium tumefaciens is the model of a critical integrator of several different external signal inputs necessary for the commitment to pathogenesis. it is the only system for which the input signal is known and a model for signal perception exists. Moreover, the genetic and molecular tools to manipulate the genome are in place, allowing the factors that control vir gene expression to be easily and safely controlled in the pathogenetic organism itself. To seize this opportunity, we propose an experimental plan that allows us to test a molecular model for signal perception, integration, and transmission in pathogenetic signaling. The approach utilizes a wide range of chemical, physical, and genetic methods that exploit the resources available in different laboratories at two distinct institutions. The results of these studies will place us in the position to determine how signal input is recognized, integrated, and transduced in two-component response regulators. In addition, this specific signaling system regulates the only know natural vector for inter-Kingdom gene transfer and understanding this mechanism has already and will continue to widened the range of its use in biotechnology.