PKA regulates calcineurin function through the phosphorylation of RCAN1: identification of a novel phosphorylation site

Biochemical and Biophysical Research Communications
Seon Sook KimSu Ryeon Seo

Abstract

Calcineurin is a calcium/calmodulin-dependent phosphatase that has been implicated in T cell activation through the induction of nuclear factors of activated T cells (NFAT). We have previously suggested that endogenous regulator of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA) for the control of calcineurin activity. In the present study, we characterized the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and revealed that PKA directly phosphorylated RCAN1 at the Ser 93. PKA-induced phosphorylation and the increase in the half-life of the RCAN1 protein were prevented by the substitution of Ser 93 with Ala (S93A). Furthermore, the PKA-mediated phosphorylation of RCAN1 at Ser 93 potentiated the inhibition of calcineurin-dependent pro-inflammatory cytokine gene expression by RCAN1. Our results suggest the presence of a novel phosphorylation site in RCAN1 and that its phosphorylation influences calcineurin-dependent inflammatory target gene expression.

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Citations

Jun 22, 2018·Annual Review of Biochemistry·David L Brautigan, Shirish Shenolikar
Sep 10, 2018·Biochemistry. Biokhimii︠a︡·E O TarasovaO P Balezina
Sep 29, 2018·Cell Death & Disease·Caroline DienerEckart Meese
Feb 23, 2020·Current Biology : CB·Anthony DudilotJannic Boehm
Jul 6, 2021·Frontiers in Cellular Neuroscience·Salma E Reyes-García, Martha L Escobar

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