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Cyclic AMP is both a pro‐apoptotic and anti‐apoptotic second messenger
Author(s) -
Insel P. A.,
Zhang L.,
Murray F.,
Yokouchi H.,
Zambon A. C.
Publication year - 2012
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2011.02273.x
Subject(s) - apoptosis , guanine nucleotide exchange factor , protein kinase a , microbiology and biotechnology , rap1 , second messenger system , effector , programmed cell death , kinase , biology , chemistry , signal transduction , biochemistry
AbstractThe second messenger cyclic AMP (cAMP) can either stimulate or inhibit programmed cell death (apoptosis). Here, we review examples of cell types that show pro‐apoptotic or anti‐apoptotic responses to increases in cAMP. We also show that cells can have both such responses, although predominantly having one or the other. Protein kinase A (PKA)‐promoted changes in phosphorylation and gene expression can mediate pro‐apoptotic responses, such as in murine S49 lymphoma cells, based on evidence that mutants lacking PKA fail to undergo cAMP‐promoted, mitochondria‐dependent apoptosis. Mechanisms for the anti‐apoptotic response to cAMP likely involve Epac (Exchange protein activated by cAMP), a cAMP‐regulated effector that is a guanine nucleotide exchange factor (GEF) for the low molecular weight G‐protein, Rap1. Therapeutic approaches that activate PKA‐mediated pro‐apoptosis or block Epac‐mediated anti‐apoptotisis may provide a means to enhance cell killing, such as in certain cancers. In contrast, efforts to block PKA or stimulate Epac have the potential to be useful in diseases settings (such as heart failure) associated with cAMP‐promoted apoptosis.