title: Dyrk1A-mediated phosphorylation of RCAN1 promotes the formation of insoluble RCAN1 aggregates.
abstract: The mechanisms underlying aggregate formation in age-related neurodegenerative diseases remain not well understood. Here we investigated whether dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) is involved in the formation of regulator of calcineurin 1 (RCAN1) aggregates. We show that RCAN1 self-associates and forms multimers, and that this process is promoted by the Dyrk1A-mediated phosphorylation of RCAN1 at the Thr(192) residue. Transgenic mice that overexpress the Dyrk1A exhibited lower levels of phospho-Thr(192)-RCAN1 in 10-month-old-group compared to littermate controls, when analyzed with soluble hippocampus lysates. These results suggest that the phosphorylation of RCAN1 by Dyrk1A stimulates the formation of insoluble aggregates upon aging.
authors.affiliation: Department of Biochemistry and Molecular Biology, Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Woo-Joo
authors.initials: WJ
authors.lastname: Song
authors.forename: Eun-Ah Christine
authors.initials: EA
authors.lastname: Song
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Hyung-Hwan
authors.initials: HH
authors.lastname: Baik
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Sul-Hee
authors.initials: SH
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D000097603:Dyrk Kinases
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C108612:RCAN1 protein, human
keywords: AD; Aggregation; Aging; Alzheimer's disease; DS; Down syndrome; Dyrk1A; GST; IP; Phosphorylation; RCAN1; TG; WT; dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A; glutathione-S-transferase; immunoprecipitation; pT192-RCAN1; pT212-Tau; phospho-Thr(192)-RCAN1; phospho-Thr(212)-Tau; regulator of calcineurin 1; transgenic; wild-type