Temporal phosphoproteomics reveals circuitry of phased propagation in insulin signaling

Michael Turewicz, Christine Skagen, Sonja Hartwig, Stephan Majda, Kristina Thedinga, Ralf Herwig, Christian Binsch, Delsi Altenhofen, D. Margriet Ouwens, Pia Marlene Förster, Thorsten Wachtmeister, Karl Köhrer, Torben Stermann, Alexandra Chadt, Stefan Lehr, Tobias Marschall, G. Hege Thoresen and Hadi Al-Hasani ()
Additional contact information
Michael Turewicz: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Christine Skagen: University of Oslo
Sonja Hartwig: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Stephan Majda: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Kristina Thedinga: Max-Planck-Institute for Molecular Genetics
Ralf Herwig: Max-Planck-Institute for Molecular Genetics
Christian Binsch: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Delsi Altenhofen: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
D. Margriet Ouwens: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Pia Marlene Förster: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Thorsten Wachtmeister: Heinrich Heine University Düsseldorf
Karl Köhrer: Heinrich Heine University Düsseldorf
Torben Stermann: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Alexandra Chadt: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Stefan Lehr: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty
Tobias Marschall: Heinrich Heine University Düsseldorf
G. Hege Thoresen: University of Oslo
Hadi Al-Hasani: Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Medical Faculty

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Insulin is a pleiotropic hormone that elicits its metabolic and mitogenic actions through numerous rapid and reversible protein phosphorylations. The temporal regulation of insulin’s intracellular signaling cascade is highly complex and insufficiently understood. We conduct a time-resolved analysis of the global insulin-regulated phosphoproteome of differentiated human primary myotubes derived from satellite cells of healthy donors using high-resolution mass spectrometry. Identification and tracking of ~13,000 phosphopeptides over time reveal a highly complex and coordinated network of transient phosphorylation and dephosphorylation events that can be allocated to time-phased regulation of distinct and non-overlapping subcellular pathways. Advanced network analysis combining protein-protein-interaction (PPI) resources and investigation of donor variability in relative phosphosite occupancy over time identifies novel putative candidates in non-canonical insulin signaling and key regulatory nodes that are likely essential for signal propagation. Lastly, we find that insulin-regulated phosphorylation of the pre-catalytic spliceosome complex is associated with acute alternative splicing events in the transcriptome of human skeletal muscle. Our findings highlight the temporal relevance of protein phosphorylations and suggest that synchronized contributions of multiple signaling pathways form part of the circuitry for propagating information to insulin effector sites.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56335-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56335-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56335-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().