Overexpression of Regulator of Calcineurin 1 (RCAN1/DSCR1/Adapt78) is known to inhibit the calcineurin-NFAT dependent signaling pathway. In this report, we find that activation of adenylate cyclase by forskolin increases the expression of RCAN1 through the increase of the protein's half-life. The ability of forskolin to increase the accumulation of RCAN1 protein is significantly inhibited with protein kinase A inhibitors such as KT5720 and H-89. Furthermore, forskolin targets the central and C-terminal region of RCAN1 and enhances the inhibitory effect of RCAN1 on the calcineurin-mediated activation of NFAT. Our findings provide the first evidence that the accumulation of the RCAN1 protein by cAMP acts as an important regulatory mechanism in the control of the calcineurin-dependent cellular pathway. Structured summary: MINT-7262390: PKA (uniprotkb:P22694) phosphorylates (MI:0217) RCAN1 (uniprotkb:P53805) by protein kinase assay (MI:0424).
Bibliographical noteFunding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2006-331-C00239 ), 2007 Research Grant from Kangwon National University , and by the Brain Korea 21 program . This study was also supported by grants from the Korea Science and Engineering Foundation (KOSEF) ( R11-2007-040-01005-0 ), through National Research Laboratory Program ( R04-2007-000-20014-0 ) funded by Ministry of Education, Science and Technology (MEST), and from the Korea Health 21 R&D Project ( A080551 ) funded by Ministry of Health, Welfare and Family Affairs . This work was carried out in facilities of Institute of Bioscience and Biotechnology at Kangwon National University.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology