دورية أكاديمية
Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs.
العنوان: | Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs. |
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المؤلفون: | van de Kooij B; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, United States., Creixell P; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, United States., van Vlimmeren A; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, United States., Joughin BA; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, United States., Miller CJ; Department of Pharmacology, Yale School of Medicine, New Haven, United States., Haider N; Department of Medical Biophysics, University of Toronto, Toronto, Canada., Simpson CD; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Linding R; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Stambolic V; Department of Medical Biophysics, University of Toronto, Toronto, Canada.; Princess Margaret Cancer Center, University Health Network, Toronto, Canada., Turk BE; Department of Pharmacology, Yale School of Medicine, New Haven, United States., Yaffe MB; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, United States.; Department of Surgery, Beth Israel Deaconess Medical Center, Divisions of Acute Care Surgery, Trauma, and Critical Care and Surgical Oncology, Harvard Medical School, Boston, United States. |
المصدر: | ELife [Elife] 2019 May 24; Vol. 8. Date of Electronic Publication: 2019 May 24. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
مواضيع طبية MeSH: | Signal Transduction* , Substrate Specificity*, NIMA-Related Kinases/*metabolism, Humans ; NIMA-Related Kinases/chemistry ; Phosphorylation ; Serine/metabolism ; Threonine/metabolism |
مستخلص: | 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 phospho-motif amplifiers of Plk1 signaling. Competing Interests: Bv, PC, Av, BJ, CM, NH, CS, RL, VS, BT, MY No competing interests declared (© 2019, van de Kooij et al.) |
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معلومات مُعتمدة: | P30-CA14051 United States CA NCI NIH HHS; R01 ES015339 United States ES NIEHS NIH HHS; T32 GM007324 United States GM NIGMS NIH HHS; P30 CA014051 United States CA NCI NIH HHS; R35 ES028374 United States ES NIEHS NIH HHS; P01 DK057751 United States DK NIDDK NIH HHS; R01-GM104047 United States NH NIH HHS; FP/2007-2013 ERC grant (KINOMEDRIFT) International European Union Seventh Framework Programme; R35-ES028374 United States NH NIH HHS; K99CA226396 United States CA NCI NIH HHS; P30-ES002109 United States ES NIEHS NIH HHS; R01 GM104047 United States GM NIGMS NIH HHS; P30 ES002109 United States ES NIEHS NIH HHS; K99 CA226396 United States CA NCI NIH HHS; BUIT 2015-7546 International Dutch Cancer Society; R01-ES015339 United States NH NIH HHS |
فهرسة مساهمة: | Keywords: Nek kinase family; Nima-related kinase; biochemistry; cancer biology; chemical biology; kinase biology; mitosis; none; signaling; substrate specificity |
المشرفين على المادة: | 2ZD004190S (Threonine) 452VLY9402 (Serine) EC 2.7.11.1 (NIMA-Related Kinases) |
تواريخ الأحداث: | Date Created: 20190525 Date Completed: 20200218 Latest Revision: 20200309 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC6570481 |
DOI: | 10.7554/eLife.44635 |
PMID: | 31124786 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2050-084X |
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DOI: | 10.7554/eLife.44635 |