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PKA‐RSK1 Interaction Modulates RSK1 Activity and Cellular Apoptosis
Author(s) -
Chaturvedi Deepti,
Cohen Michael S.,
Taunton Jack,
Patel Tarun B.
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.645.13
Subject(s) - phosphorylation , protein kinase a , microbiology and biotechnology , protein subunit , cytosol , kinase , gene silencing , biology , chemistry , biochemistry , enzyme , gene
Cyclic AMP dependent protein kinase (PKA) and ribosomal S6 kinase 1 (RSK1) share several cellular proteins as substrates. Previously, we showed novel interactions between RSK1 and the subunits of the PKA (Chaturvedi et al., Mol. Cell. Biol. 2006, Vol. 26, 4586–4600) that regulate the activity of PKA and cellular distribution of RSK1 as well as phosphorylation of RSK1 substrates. Using small inhibitory RNA (siRNA) against subunits of PKA (RI and PKAc) we have examined the role of PKA‐RSK1 interactions in regulation of RSK1 activity and apoptosis. In mouse lung fibroblast (B82L) cells, silencing of the RI subunit of PKA increases the phosphorylation of RSK1 whereas, silencing of PKAc results in decrease in phosphorylation of RSK1 in response to EGF. These changes in phosphorylation status of RSK1 are accompanied by the changes in kinase activity of the enzyme. Further, silencing of either the regulatory or catalytic subunit of PKA decreases the nuclear accumulation of active RSK1 and increases its cytosolic content in response to EGF. These changes in subcellular redistribution of active RSK1 were accompanied by decreased cellular proliferation and increased phosphorylation of its cytosolic substrate BAD with a resultant increase in the anti‐apoptotic actions of EGF. Our data also show that silencing of RI subunit increases the activity of PKA with a resultant increase in phosphorylation of PKA substrates including BAD (at Ser 155) and thus contributing in the protection of cells against apoptosis under basal conditions. Thus, we conclude that RSK1 interactions with the subunits of PKA play an important role in the regulation of RSK1 activity and its subsequent biological actions. Supported by NIH grants GM 079226