Uncovering the signaling architecture in protein-protein interaction (PPI) can certainly benefit the understanding of disease mechanisms and promise to facilitate the therapeutic interventions. Therefore, it is important to reveal the signaling relationship from one protein to another in terms of activation and inhibition. In this study, we propose a new measurement to characterize the regulation relationship of a PPI pair. By utilizing both Gene Ontology (GO) functional annotation and protein domain information, we developed a tool called Prediction of Activation/Inhibition Regulation Signaling Pathway (PAIRS) that takes protein interaction pairs as input and gives both known and predicted result of the human protein regulation relationship in terms of activation and inhibition. It helps to give prognostic regulation information for further signaling pathway reconstruction.