The Okur-Chung Neurodevelopmental Syndrome Mutation CK2^K198R Leads to a Rewiring of Kinase Specificity.

ABSTRACT: Okur-Chung Neurodevelopmental Syndrome (OCNDS) is caused by heterozygous mutations to the CSNK2A1 gene, which encodes the alpha subunit of protein kinase CK2. The most frequently occurring mutation is lysine 198 to arginine (K198R). To investigate the impact of this mutation, we first generated a high-resolution phosphorylation motif of CK2^WT, including the first characterization of specificity for tyrosine phosphorylation activity. A second high resolution motif representing CK2^K198R substrate specificity was also generated. Here we report the impact of the OCNDS associated CK2^K198R mutation. Contrary to prior speculation, the mutation does not result in a complete loss of function, but rather shifts the substrate specificity of the kinase. Broadly

SUBMITTER: Caefer DM 

PROVIDER: S-EPMC9062000 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature