PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis.

Journal article


Yadav, V. 2017. PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis. Cell discovery. Vol 3 (2017, Article: 17027). https://doi.org/10.1038/celldisc.2017.27
AuthorsYadav, V.
Abstract

Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B'-family PP2A regulatory subunits and holoenzymes. The B'-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B'α-binding motifs serve as common binding sites for B' subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions. Hundreds of proteins in the human proteome harbor intrinsic or phosphorylation-responsive B'-interaction motifs, and localize at distinct cellular organelles, such as midbody, predicting kinase-facilitated recruitment of PP2A-B' holoenzymes for tight spatiotemporal control of phosphorylation at mitosis and cytokinesis. Moroever, Polo-like kinase 1-mediated phosphorylation of Cyk4/RACGAP1, a centralspindlin component at the midbody, facilitates binding of both RhoA guanine nucleotide exchange factor (epithelial cell transforming sequence 2 (Ect2)) and PP2A-B' that in turn dephosphorylates Cyk4 and disrupts Ect2 binding. This feedback signaling loop precisely controls RhoA activation and specifies a restricted region for cleavage furrow ingression. Our results provide a framework for further investigation of diverse signaling circuits formed by PP2A-B' holoenzymes in various cellular processes.

KeywordsPP2A; Substrate Binding; Holoenzymes; Signalling
Year2017
JournalCell discovery
Journal citationVol 3 (2017, Article: 17027)
PublisherNature
ISSN2056-5968
Digital Object Identifier (DOI)https://doi.org/10.1038/celldisc.2017.27
Web address (URL)https://europepmc.org/articles/PMC5586252
Output statusPublished
Publication dates08 Aug 2017
Publication process dates
Accepted12 Jul 2017
Deposited15 Jun 2023
Permalink -

https://repository.derby.ac.uk/item/9z4x8/pp2a-b-holoenzyme-substrate-recognition-regulation-and-role-in-cytokinesis

  • 11
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Elucidation of Short linear motif based interactions and dynamics of the ezrin, radixin, moesin and merlin FERM domains
Muhammad Ali, Alisa Khramushin, Yadav, V., Ora Schueler-Furman and Ylva Ivarsson 2023. Elucidation of Short linear motif based interactions and dynamics of the ezrin, radixin, moesin and merlin FERM domains. Biochemistry. Vol 62 (Issue 11), p. 1594–1607. https://doi.org/10.1021/acs.biochem.3c00096
Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin
Ali, M., Khramushin, A., Yadav, V.K., Schueler-Furman, O. and Ivarsson, Y. 2023. Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin. Biochemistry. pp. 1-14. https://doi.org/10.1021/acs.biochem.3c00096
Polypeptides that interact with peptide tags at loops or termini and uses thereof
Yadav, V. 2022. Polypeptides that interact with peptide tags at loops or termini and uses thereof. WO2022214795A1
Advanced downstream purification of high value biopharmaceuticals
Yadav, VK 2022. Advanced downstream purification of high value biopharmaceuticals. HVB/BBNet ECR Workshop.
Positive and negative effects of graphite flake and monolayer graphene oxide templates on protein crystallization
Lin, Z., Tian, W., Yadav, V. K. and Yang, H. 2022. Positive and negative effects of graphite flake and monolayer graphene oxide templates on protein crystallization. Particuology. pp. 1-8. https://doi.org/10.1016/j.partic.2022.10.014
Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition
Li, Y., Balakrishnan, Vijaya Kumar . K., Rowse, M., Wu, C, G., Bravos, A. P., Yadav, VK, Ivarsson, Y., Strack, S., Novikova, I. V. and Xing, Y. 2022. Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition. Elife. 11, pp. 1-26. https://doi.org/10.7554/eLife.79736
DogCatcher allows loop-friendly protein-protein ligation
Heeble, A. H., Yadav, VK, Ferla, M. P., Bauer, C. C., Chuntharpursat-Bon, C., Huang, J., Bon, R. S. and Howarth, M. 2022. DogCatcher allows loop-friendly protein-protein ligation. Cell Chemical Biology. 29 (2), p. 339–350. https://doi.org/10.1016/j.chembiol.2021.07.005
Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.
Yadav, V. 2020. Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling. Molecular cell. Vol 79 (Issue 2), pp. 342-358. https://doi.org/10.1016/j.molcel.2020.06.029
Synthetic toolbox adapted from bacterial superglues to staple proteins in modular assemblies
Yadav, V. 2019. Synthetic toolbox adapted from bacterial superglues to staple proteins in modular assemblies. Protein Engineering II: from new new molecules to new processes. York, UK 15 - 17 Jul 2019 Fluidic Analytics.
Orthogonal toolbox of bacterial superglues for covalent interactions
Yadav, V. 2019. Orthogonal toolbox of bacterial superglues for covalent interactions. Synthetic Biology UK 2019. University of Warwick 09 - 10 Dec 2019 Biochemical society.
Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome.
Yadav, V. 2016. Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome. The FEBS journal. Vol 284 (Issue 3), pp. 485-498. https://doi.org/10.1111/febs.13995
Systematic discovery of Short Linear Motifs decodes hippo pathway signalling
Yadav, V. 2016. Systematic discovery of Short Linear Motifs decodes hippo pathway signalling. The modularity of signalling proteins and networks, EMBO workshop. Seefeld in Tirol, Austria 20 - 25 Sep 2016 EMBO Workshop.
Structural and binding studies of SAP-1 protein with heparin.
Yadav, V. 2014. Structural and binding studies of SAP-1 protein with heparin. Chemical biology & drug design. Vol 85 (Issue 3), pp. 404 - 410. https://doi.org/10.1111/cbdd.12420