PSKH1 kinase activity is differentially modulated via allosteric binding of Ca²⁺ sensor proteins.

ABSTRACT: Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a "dark" kinase. Here, we used biochemistry and mass spectrometry to define PSKH1's consensus substrate motif, protein interactors, and how interactors, including Ca²⁺ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca²⁺-Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca²⁺ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In addition to antagonistic

SUBMITTER: Horne CR 

PROVIDER: S-EPMC11873932 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature