Protein kinase A phosphorylates Down syndrome critical region 1 (RCAN1)

Biochem Biophys Res Commun. 2012 Feb 24;418(4):657-61. doi: 10.1016/j.bbrc.2012.01.071. Epub 2012 Jan 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / metabolism
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins
  • Down Syndrome / enzymology*
  • Gene Knockdown Techniques
  • Half-Life
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • PC12 Cells
  • Phosphorylation
  • Rats

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • RCAN1 protein, human
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin