Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 48, Issue 5, Pages 1859-1875Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST20190338
Keywords
-
Categories
Funding
- BBSRC [BB/N015886/1, BB/J004456/1, BB/P013384/1]
- MRC-DPFS [MR/K007580/1]
- BBSRC [BB/N015886/1, BBS/E/B/000C0433] Funding Source: UKRI
Ask authors/readers for more resources
ERK5 is a protein kinase that also contains a nuclear localisation signal and a transcriptional transactivation domain. Inhibition of ERK5 has therapeutic potential in cancer and inflammation and this has prompted the development of ERK5 kinase inhibitors (ERK5i). However, few ERK5i programmes have taken account of the ERK5 transactivation domain. We have recently shown that the binding of small molecule ERK5i to the ERK5 kinase domain stimulates nuclear localisation and paradoxical activation of its transactvation domain. Other kinase inhibitors paradoxically activate their intended kinase target, in some cases leading to severe physiological consequences highlighting the importance of mitigating these effects. Here, we review the assays used to monitor ERK5 activities (kinase and transcriptional) in cells, the challenges faced in development of small molecule inhibitors to the ERK5 pathway, and classify the molecular mechanisms of paradoxical activation of protein kinases by kinase inhibitors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available