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|a Van de Kooij, Bert
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|a Massachusetts Institute of Technology. Department of Biology
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|a Massachusetts Institute of Technology. Department of Biological Engineering
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Creixell Morera, Pau
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|a Van Vlimmeren, Anne Elise
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|a Joughin, Brian Alan
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|a Yaffe, Michael B
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|a Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs
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|b eLife Sciences Publications, Ltd,
|c 2020-05-27T17:03:25Z.
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|z Get fulltext
|u https://hdl.handle.net/1721.1/125507
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|a © van de Kooij et al. Human NimA-related kinases (Neks) have multiple mitotic and non-mitotic functions, but few substrates are known. We systematically determined the phosphorylation-site motifs for the entire Nek kinase family, except for Nek11. While all Nek kinases strongly select for hydrophobic residues in the -3 position, the family separates into four distinct groups based on specificity for a serine versus threonine phospho-acceptor, and preference for basic or acidic residues in other positions. Unlike Nek1-Nek9, Nek10 is a dual-specificity kinase that efficiently phosphorylates itself and peptide substrates on serine and tyrosine, and its activity is enhanced by tyrosine auto-phosphorylation. Nek10 dual-specificity depends on residues in the HRD+2 and APE- 4 positions that are uncommon in either serine/threonine or tyrosine kinases. Finally, we show that the phosphorylation-site motifs for the mitotic kinases Nek6, Nek7 and Nek9 are essentially identical to that of their upstream activator Plk1, suggesting that Nek6/7/9 function as phosphomotif amplifiers of Plk1 signaling.
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|a Dutch Cancer Society (Grant BUIT 2015-7546)
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|a National Cancer Institute (U.S.) (Grant K99CA226396)
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|a National Institutes of Health (U.S.) (Grant 01-GM104047)
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|a National Institutes of Health (U.S.) (Grant 01-ES015339)
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|a National Institutes of Health (U.S.) (Grant R35-ES028374)
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|a National Cancer Institute (U.S.) (Grant P30-CA14051)
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|a National Institute of Environmental Health Sciences (Grant P30-ES002109)
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|a en
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|a Article
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|t eLife
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