title: Global analysis of phosphorylation networks in humans.
abstract: Phosphorylation-mediated signaling plays a crucial role in nearly every aspect of cellular physiology. A recent study based on protein microarray experiments identified a large number of kinase-substrate relationships (KSRs), and built a comprehensive and reliable phosphorylation network in humans. Analysis of this network, in conjunction with additional resources, revealed several key features. First, comparison of the human and yeast phosphorylation networks uncovered an evolutionarily conserved signaling backbone dominated by kinase-to-kinase relationships. Second, although most of the KSRs themselves are not conserved, the functions enriched in the substrates for a given kinase are often conserved. Third, the prevalence of kinase-transcription factor regulatory modules suggests that phosphorylation and transcriptional regulatory networks are inherently wired together to form integrated regulatory circuits. Overall, the phosphorylation networks described in this work promise to offer new insights into the properties of kinase signaling pathways, at both the global and the protein levels. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.
authors.affiliation: Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Hu
authors.forename: Hee-Sool
authors.initials: HS
authors.lastname: Rho
authors.forename: Robert H
authors.initials: RH
authors.lastname: Newman
authors.forename: Woochang
authors.initials: W
authors.lastname: Hwang
authors.forename: John
authors.initials: J
authors.lastname: Neiswinger
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
mesh_terms: D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D006801:Humans; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D049490:Systems Biology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors; D010770:Phosphotransferases
keywords: Conservation; Kinase–substrate relationships (KSRs); Network module; Phosphorylation network