Unknown

Dataset Information

0

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.

SUBMITTER: Pearson AJ 

PROVIDER: S-EPMC7037328 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Discovery of a Gatekeeper Residue in the C-Terminal Tail of the Extracellular Signal-Regulated Protein Kinase 5 (ERK5).

Pearson Adam J AJ   Fullwood Paul P   Toro Tapia Gabriela G   Prise Ian I   Smith Michael P MP   Xu Qiuping Q   Jordan Allan A   Giurisato Emanuele E   Whitmarsh Alan J AJ   Francavilla Chiara C   Tournier Cathy C  

International journal of molecular sciences 20200131 3


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<i>,</i> we sought to elucidate the significance of phosphoacceptor sites in the C-terminal transactivation domain of ERK5. We have found that Thr<sup>732</sup> acted as a functional gatekeeper residue controlling C-terminal-mediated nuclear translocation and transcripti  ...[more]

Similar Datasets

2020-01-31 | PXD014028 | Pride
| S-EPMC3605678 | biostudies-literature
| S-EPMC2777131 | biostudies-literature
| S-EPMC2835149 | biostudies-literature
| S-EPMC3268412 | biostudies-literature
| S-EPMC2797148 | biostudies-literature
| S-EPMC1356576 | biostudies-literature
| S-EPMC240691 | biostudies-literature
| S-EPMC1223423 | biostudies-other
| S-EPMC8106020 | biostudies-literature