title: From Phosphosites to Kinases.
abstract: Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations aim to understand the global signaling modulation that takes place in different biological conditions investigated. For phosphoproteomics data, identifying the kinases central to mediating this response is key. This has prompted several efforts to catalogue the immense amounts of phosphorylation data and known or predicted kinases responsible for the modifications. However, barely 20 % of the known phosphosites are assigned to a kinase, initiating various bioinformatics efforts that attempt to predict the responsible kinases. These algorithms employ different approaches to predict kinase consensus sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available bioinformatics tools. This chapter summarizes the use of the larger phosphorylation databases, and approaches that can be applied to predict kinases that phosphorylate individual sites or that are globally modulated in phosphoproteomics datasets.
authors.affiliation: Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, Bldg. 6.2, 2200, Copenhagen, Denmark.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Munk
authors.affiliation: Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, Bldg. 6.2, 2200, Copenhagen, Denmark.|Disease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, Bldg. 6.2, 2200, Copenhagen, Denmark.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Refsgaard
authors.affiliation: Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, Bldg. 6.2, 2200, Copenhagen, Denmark.
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.affiliation: Disease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, Bldg. 6.2, 2200, Copenhagen, Denmark. lars.juhl.jensen@cpr.ku.dk.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Jensen
mesh_terms: D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D030562:Databases, Protein; D057166:High-Throughput Screening Assays; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D012984:Software; D013379:Substrate Specificity; D057188:Workflow
chemical_list: D010750:Phosphoproteins; D011494:Protein Kinases
keywords: Kinases; NetPhorest; NetworKIN; PHOSIDA; PhoshoSitePlus; Phospho.ELM; Phosphoproteomics