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

Seon Sook Kim; Yohan Oh; Kwang Chul Chung; Su Ryeon Seo

doi:10.1016/j.bbrc.2012.01.071

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

Seon Sook Kim, Yohan Oh, Kwang Chul Chung, Su Ryeon Seo

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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.

Original language	English
Pages (from-to)	657-661
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	418
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2012.01.071
Publication status	Published - 2012 Feb 24

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0065231 and 2010-0023815) and by the Brain Korea 21 program. This work was conducted in the facilities of the Institute of Bioscience and Biotechnology at Kangwon National University.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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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.",

author = "Kim, {Seon Sook} and Yohan Oh and Chung, {Kwang Chul} and Seo, {Su Ryeon}",

note = "Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0065231 and 2010-0023815) and by the Brain Korea 21 program. This work was conducted in the facilities of the Institute of Bioscience and Biotechnology at Kangwon National University.",

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AU - Kim, Seon Sook

AU - Oh, Yohan

AU - Chung, Kwang Chul

AU - Seo, Su Ryeon

N1 - Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0065231 and 2010-0023815) and by the Brain Korea 21 program. This work was conducted in the facilities of the Institute of Bioscience and Biotechnology at Kangwon National University.

PY - 2012/2/24

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N2 - 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.

AB - 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.

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

Abstract

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