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Cyclic‐AMP‐dependent protein kinase A regulates apoptosis by stabilizing the BH3‐only protein Bim
Author(s) -
Moujalled Diane,
Weston Ross,
Anderton Holly,
Ninnis Robert,
Goel Pranay,
Coley Andrew,
Huang David CS,
Wu Li,
Strasser Andreas,
Puthalakath Hamsa
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.190
Subject(s) - protein kinase a , phosphorylation , microbiology and biotechnology , protein subunit , gene isoform , kinase , ask1 , biology , protein kinase domain , mitogen activated protein kinase kinase , autophagy related protein 13 , biochemistry , chemistry , mutant , gene
The proapoptotic Bcl2 homology domain 3(BH3)‐only protein Bim is controlled by stringent post‐translational regulation, predominantly through alterations in phosphorylation status. To identify new kinases involved in its regulation, we carried out a yeast two‐hybrid screen using a non‐spliceable variant of the predominant isoform—Bim EL —as the bait and identified the regulatory subunit of cyclic‐AMP‐dependent protein kinase A—PRKAR1A—as an interacting partner. We also show that protein kinase A (PKA) is a Bim EL isoform‐specific kinase that promotes its stabilization. Inhibition of PKA or mutation of the PKA phosphorylation site within Bim EL resulted in its accelerated proteasome‐dependent degradation. These results might have implications for human diseases that are characterized by abnormally increased PKA activity, such as the Carney complex and dilated cardiomyopathy.