Involvement of the Ca2+-dependent phosphatase calcineurin in gene transcription that is stimulated by cAMP through cAMP response elements

M. Schwaninger, R. Blume, M. Kruger, G. Lux, E. Oetjen, W. Knepel*

*Corresponding author for this work
80 Citations (Scopus)

Abstract

Gene transcription can be induced by cAMP and Ca2+ through distinct protein kinases phosphorylating the transcription factor CREB, which hinds to cAMP response elements (CREs) in various genes. Induction of gene transcription by Ca2+ has been shown recently to depend on the Ca2+/calmodulin-dependent protein phosphatase calcineurin in pancreatic islet cells. This study investigates the role of calcineurin in CRE-directed gene transcription after stimulation by cAMP. Reporter fusion genes under the transcriptional control of CREs were transiently transfected into the cell line HIT. Pharmacological evidence suggests that cAMP stimulates CRE- mediated transcription through a Ca2+-dependent mechanism. The immunosuppressive drugs cyclosporin A and FK506 inhibited CRE-mediated transcription stimulated by cAMP. At the same concentrations they also inhibited calcineurin phosphatase activity. Reversal of calcineurin inhibition by rapamycin or overexpression of calcineurin led to disinhibition of CRE-mediated gene transcription. Immunoblots with a phosphoCREB-specific antibody showed that cyclosporin A and FK506 do not interfere with CREB phosphorylation at serine 119 stimulated with cAMP or membrane depolarization. These results indicate that in HIT cells stimulation of CRE-mediated transcription depends not only on the activity of protein kinases phosphorylating CREB but also on the Ca2+/calmodulin- dependent protein phosphatase calcineurin that is necessary for the transcriptional competence of phosphorylated CREB.

Original languageEnglish
JournalJournal of Biological Chemistry
Volume270
Issue number15
Pages (from-to)8860-8866
Number of pages7
ISSN0021-9258
DOIs
Publication statusPublished - 1995

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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