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Mutational analysis of two residues in the DYRK homology box of the protein kinase DYRK1A.

ABSTRACT: OBJECTIVE:Dual specificity tyrosine phosphorylation-regulated kinases (DYRK) contain a characteristic sequence motif (DYRK homology box, DH box) that is located N-terminal of the catalytic domain and supports the autophosphorylation of a conserved tyrosine during maturation of the catalytic domain. Two missense mutations in the DH box of human DYRK1B were recently identified as causative of a rare familiar form of metabolic syndrome. We have recently shown that these amino acid exchanges impair maturation of the kinase domain. Here we report the characterization of DYRK1A point mutants (D138P, K150C) that correspond to the pathogenic DYRK1B variants (H90P, R102C). RESULTS:When expressed in HeLa cells, DYRK1A-D138P and K150C showed no significant difference from wild type DYRK1A regarding the activating tyrosine autophosphorylation or catalytic activity towards exogenous substrates. However, both DYRK1A variants were underphosphorylated on tyrosine when expressed in a bacterial cell free in vitro translation system. These results suggest that D138 and K150 participate in the maturation of the catalytic domain of DYRK1A albeit the mutation of these residues is compensated under physiological conditions.

SUBMITTER: Widowati EW

PROVIDER: S-EPMC5952693 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Mutational analysis of two residues in the DYRK homology box of the protein kinase DYRK1A.

Widowati Esti Wahyu EW Bamberg-Lemper Simone S Becker Walter W

BMC research notes 20180515 1

<h4>Objective</h4>Dual specificity tyrosine phosphorylation-regulated kinases (DYRK) contain a characteristic sequence motif (DYRK homology box, DH box) that is located N-terminal of the catalytic domain and supports the autophosphorylation of a conserved tyrosine during maturation of the catalytic domain. Two missense mutations in the DH box of human DYRK1B were recently identified as causative of a rare familiar form of metabolic syndrome. We have recently shown that these amino acid exchanges ...[more]

PMID: 29764512

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Dataset Information

Mutational analysis of two residues in the DYRK homology box of the protein kinase DYRK1A.

Publications

Mutational analysis of two residues in the DYRK homology box of the protein kinase DYRK1A.

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