Protein kinase CK2 phosphorylates a conserved motif in the Notch effector E(spl)-Mγ

Autor: Ashok P. Bidwai, Lucas M. Jozwick
Rok vydání: 2022
Předmět:
Zdroj: Molecular and Cellular Biochemistry. 478:781-790
ISSN: 1573-4919
0300-8177
Popis: Across metazoans, the effects of Notch signaling are mediated via the Enhancer of Split (E(spl)/HES) basic Helix-Loop-Helix-Orange (bHLH-O) repressors. Although conserved, sequence diversity is, in large part, restricted to the C-terminal domain (CtD), which separates the O-domain from the penultimate WRPW motif that binds the co-repressor Groucho. While the kinases CK2 and MAPK target the CtD and regulate Drosophila E(spl)-M8 and mammalian HES6, the generality of this regulation to other E(spl)/HES repressors has remained unknown. To determine the broader impact of phosphorylation on this large family of repressors, we conducted bioinformatics, evolutionary and biochemical analyses. Our studies identify E(spl)-Mγ as a new target of native CK2 purified from Drosophila embryos, reveal that phosphorylation is specific to CK2 and independent of the regulatory CK2-β subunit, and identify that the site of phosphorylation is juxtaposed to the WRPW motif, a feature unique to and conserved in the Mγ homologues over 50x106 years of Drosophila evolution. Thus, a preponderance of E(spl) homologues in Drosophila are targets for CK2, and the distinct positioning of the CK2 and MAPK sites, raises the prospect that phosphorylation underlies functional diversity of bHLH-O proteins.
Databáze: OpenAIRE
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