Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Comprehensive Substrate Specificity Profiling of the Human Nek Kinome Reveals Unexpected Signaling Outputs

Bert van de Kooij, Pau Creixell, Anne van Vlimmeren, View ORCID ProfileBrian A. Joughin, Chad J. Miller, Nasir Haider, Rune Linding, View ORCID ProfileVuk Stambolic, Benjamin E. Turk, View ORCID ProfileMichael B. Yaffe
doi: https://doi.org/10.1101/515221
Bert van de Kooij
1Koch Institute for Integrative Cancer Research, MIT Center for Precision Cancer Medicine, Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pau Creixell
1Koch Institute for Integrative Cancer Research, MIT Center for Precision Cancer Medicine, Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne van Vlimmeren
1Koch Institute for Integrative Cancer Research, MIT Center for Precision Cancer Medicine, Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian A. Joughin
1Koch Institute for Integrative Cancer Research, MIT Center for Precision Cancer Medicine, Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Brian A. Joughin
Chad J. Miller
2Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nasir Haider
3Department of Medical Biophysics, University of Toronto, Toronto, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rune Linding
4Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vuk Stambolic
3Department of Medical Biophysics, University of Toronto, Toronto, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vuk Stambolic
Benjamin E. Turk
2Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael B. Yaffe
1Koch Institute for Integrative Cancer Research, MIT Center for Precision Cancer Medicine, Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA
5Department of Surgery, Beth Israel Deaconess Medical Center, Divisions of Acute Care Surgery, Trauma, and Critical Care and Surgical Oncology, Harvard Medical School, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael B. Yaffe
  • For correspondence: myaffe@mit.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

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.

Footnotes

  • ↵Department of Biochemistry, University of Washington, Seattle, WA, USA

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted January 08, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Comprehensive Substrate Specificity Profiling of the Human Nek Kinome Reveals Unexpected Signaling Outputs
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Comprehensive Substrate Specificity Profiling of the Human Nek Kinome Reveals Unexpected Signaling Outputs
Bert van de Kooij, Pau Creixell, Anne van Vlimmeren, Brian A. Joughin, Chad J. Miller, Nasir Haider, Rune Linding, Vuk Stambolic, Benjamin E. Turk, Michael B. Yaffe
bioRxiv 515221; doi: https://doi.org/10.1101/515221
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Comprehensive Substrate Specificity Profiling of the Human Nek Kinome Reveals Unexpected Signaling Outputs
Bert van de Kooij, Pau Creixell, Anne van Vlimmeren, Brian A. Joughin, Chad J. Miller, Nasir Haider, Rune Linding, Vuk Stambolic, Benjamin E. Turk, Michael B. Yaffe
bioRxiv 515221; doi: https://doi.org/10.1101/515221

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Subject Areas
All Articles
  • Animal Behavior and Cognition (3520)
  • Biochemistry (7373)
  • Bioengineering (5357)
  • Bioinformatics (20357)
  • Biophysics (10059)
  • Cancer Biology (7790)
  • Cell Biology (11361)
  • Clinical Trials (138)
  • Developmental Biology (6457)
  • Ecology (9995)
  • Epidemiology (2065)
  • Evolutionary Biology (13376)
  • Genetics (9379)
  • Genomics (12625)
  • Immunology (7735)
  • Microbiology (19122)
  • Molecular Biology (7482)
  • Neuroscience (41201)
  • Paleontology (301)
  • Pathology (1236)
  • Pharmacology and Toxicology (2146)
  • Physiology (3191)
  • Plant Biology (6887)
  • Scientific Communication and Education (1277)
  • Synthetic Biology (1901)
  • Systems Biology (5332)
  • Zoology (1091)