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Role of Gravin Scaffolding of PKC Signaling in the Heart
Author(s) -
Singh Sonal,
Guillory Ashley,
Wijaya Cori,
McConnell Bradley K.
Publication year - 2013
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.27.1_supplement.lb558
Subject(s) - protein kinase c , phosphorylation , agonist , stimulation , signal transduction , microbiology and biotechnology , chemistry , desensitization (medicine) , scaffold protein , receptor , knockout mouse , medicine , endocrinology , biology , biochemistry
Gravin, an A kinase anchoring protein, scaffolds p r o t e i n k i n a s e A ( PKA), protein kinase C (PKC), and other signaling molecules to the β2‐adrenergic receptor (AR). Agonist stimulation of β2‐AR leads to gravin‐dependent desensitization of the receptor. Disruption of PKA/AKAP interaction or suppression of gravin expression disrupts β2‐AR desensitization by PKC phosphorylation. The objective of this study was to investigate the role of PKC on cardiac function in the absence of gravin mediated scaffolding. Total PKC activity was determined in wild‐type and gravin knockout mice stimulated with isoproterenol (30mg/kg/day) for 14‐days. Basal PKC activity was significantly increased in the KO animals. Additionally, PKC activity significantly increased in both WT and KO ISO groups compared to their respective controls. PKC activity was also found to be greater in the KO ISO group as compared to both the KO and the WT controls (p<0.0001). However, despite of the changes in PKC activity, no change in the expression of PKCα was seen in the KO mice, either before or after ISO treatment. Hence in the absence of scaffolding mediated by gravin, there is an increase in the PKC activity without a corresponding change in PKCα expression or phosphorylation. Further investigation is being carried out using PKC activators and inhibitors to determine the interplay between gravin and PKC in modulating the PKC signaling in heart. Source of research support was RO1HL085487.