Molecular Systems Biology | |
Construction of human activity‐based phosphorylation networks | |
Robert H Newman8  Jianfei Hu3  Hee-Sool Rho8  Zhi Xie3  Crystal Woodard8  John Neiswinger8  Christopher Cooper7  Matthew Shirley8  Hillary M Clark8  Shaohui Hu8  Woochang Hwang3  Jun Seop Jeong8  George Wu11  Jimmy Lin14  Xinxin Gao8  Qiang Ni8  Renu Goel2  Shuli Xia6  Hongkai Ji11  Kevin N Dalby5  Morris J Birnbaum12  Philip A Cole8  Stefan Knapp1,8  Alexey G Ryazanov8,9  Donald J Zack3  Seth Blackshaw8,10  Tony Pawson8,13  Anne-Claude Gingras8,13  Stephen Desiderio7  Akhilesh Pandey7  Benjamin E Turk4,8  Jin Zhang8  Heng Zhu8  | |
[1] Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Oxford, UK;Institute of Bioinformatics, International Tech Park, Bangalore, India;Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA;Division of Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX, USA;Hugo W. Moser Kennedy Krieger Institute, Baltimore, MD, USA;Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA;Center for High-Throughput Biology, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital Toronto, ON, Canada;The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA | |
关键词: phosphorylation; signaling networks; systems biology; | |
DOI : 10.1038/msb.2013.12 | |
来源: Wiley | |
【 摘 要 】
The landscape of human phosphorylation networks has not been systematically explored, representing vast, unchartered territories within cellular signaling networks. Although a large number of in vivo phosphorylated residues have been identified by mass spectrometry (MS)-based approaches, assigning the upstream kinases to these residues requires biochemical analysis of kinase-substrate relationships (KSRs). Here, we developed a new strategy, called CEASAR, based on functional protein microarrays and bioinformatics to experimentally identify substrates for 289 unique kinases, resulting in 3656 high-quality KSRs. We then generated consensus phosphorylation motifs for each of the kinases and integrated this information, along with information about in vivo phosphorylation sites determined by MS, to construct a high-resolution map of phosphorylation networks that connects 230 kinases to 2591 in vivo phosphorylation sites in 652 substrates. The value of this data set is demonstrated through the discovery of a new role for PKA downstream of Btk (Bruton's tyrosine kinase) during B-cell receptor signaling. Overall, these studies provide global insights into kinase-mediated signaling pathways and promise to advance our understanding of cellular signaling processes in humans. A high-resolution map of human phosphorylation networks was constructed by integrating experimentally determined kinase-substrate relationships with other resources, such as in vivo phosphorylation sites.Abstract
Synopsis
【 授权许可】
CC BY-NC-SA
Copyright © 2013 EMBO and Macmillan Publishers Limited
Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202107150008284ZK.pdf | 674KB | download |