title: Toward a systems-level view of dynamic phosphorylation networks.
abstract: To better understand how cells sense and respond to their environment, it is important to understand the organization and regulation of the phosphorylation networks that underlie most cellular signal transduction pathways. These networks, which are composed of protein kinases, protein phosphatases and their respective cellular targets, are highly dynamic. Importantly, to achieve signaling specificity, phosphorylation networks must be regulated at several levels, including at the level of protein expression, substrate recognition, and spatiotemporal modulation of enzymatic activity. Here, we briefly summarize some of the traditional methods used to study the phosphorylation status of cellular proteins before focusing our attention on several recent technological advances, such as protein microarrays, quantitative mass spectrometry, and genetically-targetable fluorescent biosensors, that are offering new insights into the organization and regulation of cellular phosphorylation networks. Together, these approaches promise to lead to a systems-level view of dynamic phosphorylation networks.
authors.affiliation: Department of Biology, North Carolina Agricultural and Technical State University Greensboro, NC, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Newman
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA ; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine Baltimore, MD, USA ; Department of Oncology, Johns Hopkins University School of Medicine Baltimore, MD, USA ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine Baltimore, MD, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA ; High-Throughput Biology Center, Institute for Basic Biomedical Sciences, Johns Hopkins University Baltimore, MD, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
keywords: cell signaling and regulation; fluorescent biosensors; kinase-substrate relationship; phosphoproteomics; protein microarrays; protein phosphorylation networks; quantitative mass spectrometry; systems biology