Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases

被引:74
作者
Buljan, Marija [1 ,2 ]
Ciuffa, Rodolfo [1 ]
van Drogen, Audrey [1 ]
Vichalkovski, Anton [1 ]
Mehnert, Martin [1 ]
Rosenberger, George [1 ,3 ]
Lee, Sohyon [1 ]
Varjosalo, Markku [4 ]
Pernas, Lucia Espona [1 ]
Spegg, Vincent [5 ]
Snijder, Berend [1 ]
Aebersold, Ruedi [1 ,6 ]
Gstaiger, Matthias [1 ]
机构
[1] Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland
[2] Empa, Swiss Fed Labs Mat Sci & Technol, CH-9014 St Gallen, Switzerland
[3] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA
[4] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland
[5] Univ Zurich, Dept Mol Mech Dis, CH-8057 Zurich, Switzerland
[6] Univ Zurich, Fac Sci, Zurich, Switzerland
关键词
TREACHER-COLLINS-SYNDROME; PROTEIN-KINASE; COMPREHENSIVE RESOURCE; AFFINITY PURIFICATION; REVEALS; PHOSPHORYLATION; IDENTIFICATION; ORGANIZATION; MUTATIONS; DISCOVERY;
D O I
10.1016/j.molcel.2020.07.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinases are essential for signal transduction and control of most cellular processes, including metabolism, membrane transport, motility, and cell cycle. Despite the critical role of kinases in cells and their strong association with diseases, good coverage of their interactions is available for only a fraction of the 535 human kinases. Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. The interaction dataset is a high-quality resource with more than 5,000 previously unreported interactions. We extensively characterized the obtained network and were able to identify previously described, as well as predict new, kinase functional associations, including those of the less well-studied kinases PIM3 and protein O-mannose kinase (POMK). Importantly, the presented interaction map is a valuable resource for assisting biomedical studies. We uncover dozens of kinase-disease associations spanning from genetic disorders to complex diseases, including cancer.
引用
收藏
页码:504 / +
页数:26
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