Global analysis of phosphorylation networks in humans

Jianfei Hu, Hee Sool Rho, Robert H. Newman, Woochang Hwang, John Neiswinger, Heng Zhu, Jin Zhang, Jiang Qian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)224-231
Number of pages8
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1844
Issue number1 PART B
DOIs
StatePublished - Jan 2014

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Keywords

  • Conservation
  • Kinase-substrate relationships (KSRs)
  • Network module
  • Phosphorylation network

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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