Letter to the editor: “Systems biology versus reductionism in cell physiology”

to the editor: The following is a response to the editorial comment of Prihandoko and Tobin (15) about our recent paper in American Journal of Physiology-Cell Physiology (2), which addresses a key question in modeling of signaling networks: How to assign the protein kinases (from the entire 521-member kinome list) that are responsible for each measurable phosphorylation event in a given cell type. In our study, we used vasopressin-stimulated phosphorylation of the water channel protein, aquaporin-2, at serine-256 as an example because of its importance to the physiology of collecting duct principal cells. We thank Prihandoko and Tobin for their thorough and well thought out summary of our paper. We write now to provide additional clarification regarding the epistemological approach, which was based on a systems biological framework rather than on reductionist principles. Understanding the two ways of doing experiments is aided by a bit of history.