Redox regulation of protein kinases.

ABSTRACT: Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous hydrogen peroxide (H?O?) by membrane-bound NADPH oxidases. In turn, H?O? can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H?O? regarding kinase activity, as well as the components involved in H?O? production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H?O? through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiological and pathological H?O? responses.

SUBMITTER: Truong TH 

PROVIDER: S-EPMC4358782 | biostudies-literature | 2013 Jul-Aug

REPOSITORIES: biostudies-literature