Redox regulation of tyrosine kinase signalling: more than meets the eye.

Abstract:

:Protein kinases are essential mediators of cellular signal transduction and are often dysregulated in disease. Among these, protein tyrosine kinases (PTKs) have received specific interest due to their common roles in various diseases including cancer, and emerging observations indicating that PTK signalling pathways are susceptible to regulation by reactive oxygen species (ROS), which are also frequently implicated in disease pathology. While it is well recognized that ROS can impact on tyrosine kinase signalling by inhibiting tyrosine phosphatases, more recent studies highlight additional modes of redox-based regulation of tyrosine kinase signalling by direct redox modification of non-catalytic cysteines within tyrosine kinases or other protein components of this signalling pathway. In this review, we will present recent advancements with respect to redox-based mechanisms in regulating PTK signalling, with a specific focus on recent studies demonstrating direct redox regulation of Src-family kinases and epidermal growth factor receptor kinases. Importantly, redox-based modulation of tyrosine kinases may be relevant for many other kinases and has implications for current approaches to develop pharmacological inhibitors for these proteins.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Dustin CM,Heppner DE,Lin MJ,van der Vliet A

doi

10.1093/jb/mvz085

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

151-163

issue

2

eissn

0021-924X

issn

1756-2651

pii

5585012

journal_volume

167

pub_type

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