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Calcineurin Binding to the mAKAPβ Signalosome
Author(s) -
Kapiloff Michael Seth,
Lopez Johanna,
Negro Alejandra,
Henson Edward,
DodgeKafka Kimberly,
Bauman Andrea
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.911.3
Subject(s) - calcineurin , nfat , transcription factor , microbiology and biotechnology , calmodulin , ryanodine receptor , myocyte , biology , protein kinase a , phosphatase , kinase , chemistry , biochemistry , phosphorylation , medicine , enzyme , transplantation , intracellular , gene
mAKAPβ is the scaffold for a signalosome located on the cardiac myocyte nuclear envelope which is believed to transduce local cAMP and calcium ion signals and to mediate crosstalk with MAP‐kinase signaling pathways. We and others have shown that mAKAPβ binds a set of signaling enzymes that includes protein kinase A, the calcium‐release channel ryanodine receptor, type 4D3 phosphodiesterase, ERK5 and MEK5, and the cAMP‐dependent rap1‐guanine exchange factor epac1. We have recently found that the calcium/calmodulin‐dependent phosphatase calcineurin binds mAKAPβ. Calcineurin is a mediator of cardiac hypertrophy in vivo and in vitro and is responsible for the dephosphorylation and activation of NFATc transcription factors. We have found that mAKAPβ expression is required for the nuclear translocation of NFATc in myocytes and for the induction of myocyte hypertrophy by adrenergic agonists. We now show that the catalytic A‐subunit of calcineurin can directly bind mAKAPβ. This binding is enhanced by calcium/calmodulin in vitro and is induced by norepinephrine treatment of cultured myocytes. Interestingly, the calcineurin binding site on mAKAPβ does not contain a consensus binding site, suggesting a novel calcineurin binding domain. We propose that by binding calcineurin, the mAKAPβ signalosome participates in the regulation of NFATc transcription factors involved in the induction of myocyte hypertrophy.