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The alpha 2A adrenergic receptor evokes activation of p70S6 kinase through G protein and transactivation of EGFR
Author(s) -
Chen Huaping,
Lu Roujian,
Wang Qin
Publication year - 2011
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.25.1_supplement.1009.1
Subject(s) - transactivation , pi3k/akt/mtor pathway , protein kinase b , pertussis toxin , microbiology and biotechnology , signal transduction , chemistry , mapk/erk pathway , stimulation , g protein , kinase , protein kinase a , biology , endocrinology , biochemistry , transcription factor , gene
The function of α 2A adrenergic receptor (α 2A AR) has been implicated in a wide range of physiological activities. The molecular mechanisms behind these activities are topics under intensive investigation. At the cellular level, stimulation of the α 2A AR leads to propagation of a number of signaling cascades, such as MAPK, Akt and p70S6 kinase (p70S6K) pathways. In the current study, we characterized α 2A AR‐mediated p70S6K activation. Stimulation of the α 2A AR evokes activation of p70S6K in both embryonic fibroblasts (MEF) and neurons in a dose‐dependent manner. To delineate the molecular pathway of the α 2A AR‐mediated p70S6K activation, pharmacological inhibitors for potential signaling molecules involved were applied on cells. Pertussis toxin treatment of cells blocked α 2A AR‐mediated p70S6K activation, indicating the involvement of G proteins in this process. When cells were treated with an EGFR inhibitor or a PI3K inhibitor, α 2A AR‐mediated p70S6K activation was also blocked. Additionally, rapamycin treatment diminished α 2A AR‐mediated p70S6K activation. Taken together, these data suggests that α 2A AR‐mediated activation of p70S6K is a G protein‐dependent process and achieved through transactivation of EGFR, which subsequently activates PI3K and mTOR to stimulate p70S6K. This research was supported by a NIH grant MH081917 (QW) and an AHA SDG grant 0630103N (QW).