Journal
FEBS JOURNAL
Volume 273, Issue 10, Pages 2100-2109Publisher
WILEY
DOI: 10.1111/j.1742-4658.2006.05217.x
Keywords
Adapt78; calcineurin; DSCR1; GSK-3 beta; RCAN1
Categories
Funding
- NIA NIH HHS [AG16256] Funding Source: Medline
Ask authors/readers for more resources
The RCAN1 protein (previously called calcipressin 1 or MCIP1) binds to calcineurin, a serine/threonine phosphatase (PP2B), and inhibits its activity. Here we demonstrate that regulated overexpression of an RCAN1transgene (this gene was previously called DSCR1 or Adapt78) also stimulates expression of the GSK-3 beta kinase, which can antagonize the action of calcineurin. We also show that GSK-3 beta is regulated by RCAN1 at a post-transcriptional level. In humans, high RCAN1 expression is found in the brain, where at least two mRNA isoforms have been reported. Therefore, we further investigated expression of the various RCAN1 isoforms, resulting from differential splicing and alternative promotors in human brain. We detected at least three distinct RCAN1s: RCAN1-1 Short at 31 kDa (RCAN1-1S), RCAN1-1 Long at 38 kDa (RCAN1-1 L), and RCAN1-4. Furthermore, the levels of RCAN1-1S, but not RCAN1-1 L or RCAN1-4 correlated with the levels of GSK-3 beta. This suggests that RCAN1-1S might induce production of GSK-3 beta in vivo. While RCAN1s can regulate calcineurin and GSK-3 beta, it has also been shown that calcineurin and GSK-3 beta can regulate RCAN1s. Here we propose a new model (incorporating all these findings) in which cells maintain an equilibrium between RCAN1s, calcineurin, and GSK-3 beta.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available