title: Protein kinase A phosphorylates Down syndrome critical region 1 (RCAN1).
abstract: The Down syndrome critical region 1 (DSCR1) gene encodes a regulator of the calcineurin 1 (RCAN1) protein, and the elevated levels of RCAN1 are associated with Alzheimer's disease (AD) and Down syndrome (DS). In this report, we found that protein kinase A (PKA) was able to phosphorylate RCAN1 in vitro and in vivo. In addition, we found that the phosphorylation of RCAN1 by PKA caused an increase of RCAN1 expression by increasing of the half-life of the protein. Consistently, the pharmacological inhibition of intracellular PKA using H-89 and the knockdown of the endogenous PKA catalytic subunit with siRNA decreased the expression of RCAN1. Furthermore, the phosphorylation of RCAN1 by PKA enhanced the inhibitory function of RCAN1 on calcineurin-mediated gene transcription. Our data provide the first evidence that PKA acts as an important regulatory component in the control of RCAN1 function through phosphorylation.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Seon Sook
authors.initials: SS
authors.lastname: Kim
authors.forename: Yohan
authors.initials: Y
authors.lastname: Oh
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
authors.forename: Su Ryeon
authors.initials: SR
authors.lastname: Seo
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000201:enzymology*; D055785:Gene Knockdown Techniques; D006207:Half-Life; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin