Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs.

Journal Article (Journal Article)

Transgenic mice were generated with cardiac-specific overexpression of the G protein-coupled receptor kinase 3 (GRK3) to explore the in vivo role of this GRK in cardiac function. GRK3 is expressed in the heart along with the β-adrenergic receptor kinase (β-ARK1) and GRK5. We have previously demonstrated that myocardial-targeted overexpression in transgenic mice of β-ARK1 (Koch, W.J., H. A. Rockman, P. Samama, R. A. Hamilton, R. A. Bond, C. A. Milano, and R. J. Lefkowitz. Science 268: 1350-1353, 1995) or GRK5 (Rockman, H.A., D.-J. Choi, N. U. Rahman, S. A. Akhter, R. J. Lefkowitz, and W. J. Koch. Proc. Natl. Acad. Sci. USA 93: 9954-9959, 1996) results in significant attenuation of β-adrenergic signaling and in vivo cardiac function and selective desensitization of angiotensin (ANG) II-mediated cardiac responses. Surprisingly, myocardial overexpression of GRK3 resulted in normal biochemical signaling through β-adrenergic receptors (β-ARs), and in vivo hemodynamic function in response to a β-AR agonist was indistinguishable from that in nontransgenic controls. Furthermore, in vivo signaling and functional responses to ANG II were unaltered. However, myocardial thrombin signaling, as assessed by p42/p44 mitogen-activated protein (MAP) kinase activation, was significantly attenuated in GRK3 transgenic mouse hearts, indicating a distinct in vivo substrate specificity for GRK3.

Full Text

Duke Authors

Cited Authors

  • Iaccarino, G; Rockman, HA; Shotwell, KF; Tomhave, ED; Koch, WJ

Published Date

  • October 1, 1998

Published In

Volume / Issue

  • 275 / 4

Start / End Page

  • H1298 - H1306

PubMed ID

  • 29586850

Electronic International Standard Serial Number (EISSN)

  • 1522-1539

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.1998.275.4.H1298


  • eng

Conference Location

  • United States