Diseases caused by altered specificity of a protein kinase for its allosteric activators.

Trends Biochem Sci

MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, Scotland, UK. Electronic address:

Published: November 2024

Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.

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Source
http://dx.doi.org/10.1016/j.tibs.2024.10.008DOI Listing

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