Interactomes of Glycogen Synthase Kinase-3 Isoforms

J Proteome Res. 2023 Mar 3;22(3):977-989. doi: 10.1021/acs.jproteome.2c00825. Epub 2023 Feb 13.


Functional differentiation of the two isoforms of the protein-serine/threonine kinase, glycogen synthase kinase-3 (GSK-3), is an unsettled area of research. The isoforms are highly similar in structure and are largely redundant, though there is also evidence for specific roles. Identification of isoform-specific protein interactors may elucidate the differences in function and provide insight into isoform-selective regulation. We therefore sought to identify novel GSK-3 interaction partners and to examine differences in the interactomes of the two isoforms using both affinity purification and proximity-dependent biotinylation (BioID) mass spectrometry methods. While the interactomes of the two isomers are highly similar in HEK293 cells, BioID in HeLa cells yielded a variety of preys that are preferentially associated with one of the two isoforms. DCP1B, which favored GSK-3α, and MISP, which favored GSK-3β, were evaluated for reciprocal interactions. The differences in interactions between isoforms may help in understanding the distinct functions and regulation of the two isoforms as well as offer avenues for the development of isoform-specific strategies.

Keywords: BioID; GSK-3; glycogen synthase kinase-3; interactomes; protein isoforms; protein−protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Protein Isoforms / genetics


  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Protein Isoforms

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