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Gravin‐Dependent Multi‐Kinase Signaling Modulates Cardiac Function
Author(s) -
Guillory Ashley Nicole,
Tran Paul,
Bilal Khadijah,
Wijaya Cori,
Diaz Andrea Diaz,
McConnell Bradley
Publication year - 2012
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.26.1_supplement.666.9
Subject(s) - phospholamban , chemistry , protein kinase c , protein kinase a , basal (medicine) , kinase , medicine , knockout mouse , phosphorylation , endocrinology , biochemistry , biology , receptor , insulin
The purpose of this study was to investigate the effect of knockout of gravin, an A kinase anchoring protein, on the regulation of cardiac function by protein kinase A (PKA) and protein kinase C (PKC). We measured PKA activity, PKC activity and PKA substrate phosphorylation in wild‐type (WT) and gravin knockout (KO) mice stimulated with isoproterenol (ISO; 30 mg/kg/day x 14 days). Basal PKA activity was significantly increased in both WT and KO mice treated with ISO (WT Vehicle: 0.023±0.0041; WT ISO: 0.098±0.021; KO Vehicle: 0.020±0.0021; KO ISO: 0.069±0.0090; A.U.; p=0.0023). However, the WT ISO and KO ISO mice had a decreased response to cAMP‐stimulated PKA activity compared to their respective controls (WT Vehicle: 0.44±0.0094; WT ISO: 0.35±0.027; KO Vehicle: 0.46±0.011; KO ISO: 0.35±0.026; A.U.; p=0.0043). Basal PKC activity was significantly increased in untreated KO animals (WT Vehicle: 0.069±0.012; KO Vehicle: 0.13±0.022; A.U.; p=0.041). Additionally, there was a significant increase in phospho‐phospholamban in the KO ISO group compared to both its control and the WT ISO group (p=0.0151). Furthermore, phospho‐troponin I was significantly increased in the WT ISO group compared to both its control and the KO ISO group (p=0.033). These data indicate that the absence of gravin has a profound effect on the activity and action of PKA and PKC. This research was supported by NIH R01HL085487.