Phosphoproteomic screening identifies physiological substrates of the CDKL5 kinase.

ABSTRACT: Mutations in the gene encoding the protein kinase CDKL5 cause a debilitating neurodevelopmental disease termed CDKL5 disorder. The impact of these mutations on CDKL5 function is poorly understood because the substrates and cellular processes controlled by CDKL5 are unclear. Here, we describe a quantitative phosphoproteomic screening which identified MAP1S, CEP131 and DLG5-regulators of microtubule and centrosome function-as cellular substrates of CDKL5. Antibodies against MAP1S phospho-Ser⁹⁰⁰ and CEP131 phospho-Ser³⁵ confirmed CDKL5-dependent phosphorylation of these targets in human cells. The phospho-acceptor serine residues in MAP1S, CEP131 and DLG5 lie in the motif RPXSA, although CDKL5 can tolerate residues other than Ala immediately C-terminal to the phos

SUBMITTER: Munoz IM 

PROVIDER: S-EPMC6293279 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature