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Calcium signaling regulates gravin‐dependent compartmentalization of PKA
Author(s) -
Schott Micah Bruce,
Grove Bryon
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.875.6
Subject(s) - bapta , microbiology and biotechnology , chemistry , biophysics , redistribution (election) , calcium , cytosol , intracellular , biochemistry , biology , enzyme , organic chemistry , politics , political science , law
Gravin (AKAP12) is a multivalent scaffolding protein that anchors PKA to the plasma membrane, but undergoes redistribution to an intracellular compartment in response to PKC activation or increased [Ca 2+ ] i . We postulate that through this mechanism gravin may mediate cross‐talk between Ca 2+ ‐dependent and cAMP‐dependent signaling pathways. To assess this, we examined the effect of Ca 2+ ‐elevating agents on gravin and gravin‐dependent PKA distribution in cells lacking endogenous gravin but expressing EGFP/ EYFP‐gravin constructs. Ionomycin and thapsigargin initiated rapid gravin redistribution into the cytosol, an event which was inhibited by Ca 2+ chelation using BAPTA‐AM. Treatment of cells coexpressing gravin‐EYFP and PKA RII‐ECFP with Ca 2+ ‐elevating agents also resulted in PKA redistribution, but only when gravin was present. Consistent with this, treatment with lysophosphatidic acid (LPA) also resulted in rapid gravin redistribution in concert with a rise in [Ca 2+ ] i and resulted in PKA redistribution in cells coexpressing gravin and PKA constructs. However, inhibition studies using BAPTA‐AM and bisindolylmaleimide suggest that in addition to changes in [Ca 2+ ] i , LPA‐mediated gravin dynamics may involve other mechanisms. Studies to further elucidate the mechanism behind LPA‐mediated gravin dynamics are currently underway. This work was supported by funding from UNDSMHS and NIH 5P20RR017699. Grant Funding Source : Institutional/NIH