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PKA‐RSK1 Interactions in Regulation of Cell Proliferation and Apoptosis
Author(s) -
Chaturvedi Deepti,
Edwin Francis,
Gao Xianlong,
Cohen Michael S,
Taunton Jack,
Patel Tarun B
Publication year - 2007
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.21.6.a805-a
Subject(s) - protein subunit , protein kinase a , cytosol , microbiology and biotechnology , phosphorylation , cell growth , kinase , chemistry , biology , biochemistry , enzyme , gene
Cyclic AMP dependent protein kinase (PKA) and ribosomal S6 kinase 1 (RSK1) share several cellular proteins as substrates. Recently, we have shown novel interactions between RSK1 and the subunits of the PKA (Chaturvedi et al., Mol. Cell. Biol. 2006, Vol. 26 , –4600) that regulate the activity of PKA and cellular distribution RSK1 as well as phosphorylation of RSK1 substrates. These interactions are modulated by the activation state of RSK1. Thus, inactive RSK1 interacts with the type I regulatory subunit (RI) and active RSK1 with catalytic subunit (PKAc) of PKA. Using small inhibitory RNA (siRNA) against subunits of PKA we have examined the role of PKA‐RSK1 interactions in regulation of cell proliferation and apoptosis. In mouse lung fibroblast (B82L) cells, 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. Studies to determine the role of the RSK1/PKA subunit interactions in the activation of RSK1 by EGF are in progress. Supported by NIH grant GM 073181