Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)Citation formats

  • External authors:
  • Adam J. Pearson
  • Paul Fullwood
  • Gabriela Toro Tapia
  • Ian Prise
  • Michael P. Smith
  • Qiuping Xu
  • Allan Jordan
  • Emanuele Giurisato

Standard

Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5). / Pearson, Adam J.; Fullwood, Paul; Tapia, Gabriela Toro; Prise, Ian; Smith, Michael P.; Xu, Qiuping; Jordan, Allan; Giurisato, Emanuele; Whitmarsh, Alan J.; Francavilla, Chiara; Tournier, Cathy.

In: International Journal of Molecular Sciences, Vol. 21, No. 3, 929, 01.02.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Pearson, AJ, Fullwood, P, Tapia, GT, Prise, I, Smith, MP, Xu, Q, Jordan, A, Giurisato, E, Whitmarsh, AJ, Francavilla, C & Tournier, C 2020, 'Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)', International Journal of Molecular Sciences, vol. 21, no. 3, 929. https://doi.org/10.3390/ijms21030929

APA

Pearson, A. J., Fullwood, P., Tapia, G. T., Prise, I., Smith, M. P., Xu, Q., Jordan, A., Giurisato, E., Whitmarsh, A. J., Francavilla, C., & Tournier, C. (2020). Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5). International Journal of Molecular Sciences, 21(3), [929]. https://doi.org/10.3390/ijms21030929

Vancouver

Pearson AJ, Fullwood P, Tapia GT, Prise I, Smith MP, Xu Q et al. Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5). International Journal of Molecular Sciences. 2020 Feb 1;21(3). 929. https://doi.org/10.3390/ijms21030929

Author

Pearson, Adam J. ; Fullwood, Paul ; Tapia, Gabriela Toro ; Prise, Ian ; Smith, Michael P. ; Xu, Qiuping ; Jordan, Allan ; Giurisato, Emanuele ; Whitmarsh, Alan J. ; Francavilla, Chiara ; Tournier, Cathy. / Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5). In: International Journal of Molecular Sciences. 2020 ; Vol. 21, No. 3.

Bibtex

@article{18879b590a474731a2d95d8295460a59,
title = "Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)",
abstract = "The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C-terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C-terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C-terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Collectively, our results firmly establish the significance of C-terminal phosphorylation in regulating ERK5 function. The post-translational modification of ERK5 on its C-terminal tail might be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated.",
keywords = "ERK5, MAPK, Mass spectrometry, Phosphorylation, Proteomics, Transcription",
author = "Pearson, {Adam J.} and Paul Fullwood and Tapia, {Gabriela Toro} and Ian Prise and Smith, {Michael P.} and Qiuping Xu and Allan Jordan and Emanuele Giurisato and Whitmarsh, {Alan J.} and Chiara Francavilla and Cathy Tournier",
year = "2020",
month = feb,
day = "1",
doi = "10.3390/ijms21030929",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",
number = "3",

}

RIS

TY - JOUR

T1 - Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)

AU - Pearson, Adam J.

AU - Fullwood, Paul

AU - Tapia, Gabriela Toro

AU - Prise, Ian

AU - Smith, Michael P.

AU - Xu, Qiuping

AU - Jordan, Allan

AU - Giurisato, Emanuele

AU - Whitmarsh, Alan J.

AU - Francavilla, Chiara

AU - Tournier, Cathy

PY - 2020/2/1

Y1 - 2020/2/1

N2 - The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C-terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C-terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C-terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Collectively, our results firmly establish the significance of C-terminal phosphorylation in regulating ERK5 function. The post-translational modification of ERK5 on its C-terminal tail might be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated.

AB - The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C-terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C-terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C-terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Collectively, our results firmly establish the significance of C-terminal phosphorylation in regulating ERK5 function. The post-translational modification of ERK5 on its C-terminal tail might be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated.

KW - ERK5

KW - MAPK

KW - Mass spectrometry

KW - Phosphorylation

KW - Proteomics

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=85079061148&partnerID=8YFLogxK

U2 - 10.3390/ijms21030929

DO - 10.3390/ijms21030929

M3 - Article

C2 - 32023819

AN - SCOPUS:85079061148

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 3

M1 - 929

ER -