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

Publication ,  Journal Article
Iaccarino, G; Rockman, HA; Shotwell, KF; Tomhave, ED; Koch, WJ
Published in: Am J Physiol Heart Circ Physiol
October 1, 1998

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.

Duke Scholars

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

October 1, 1998

Volume

275

Issue

4

Start / End Page

H1298 / H1306

Location

United States

Related Subject Headings

  • Signal Transduction
  • Rhodopsin
  • Reference Values
  • Receptors, Thrombin
  • Receptors, Adrenergic, beta
  • Receptor Protein-Tyrosine Kinases
  • Radioligand Assay
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Peptide Fragments
 

Citation

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Iaccarino, G., Rockman, H. A., Shotwell, K. F., Tomhave, E. D., & Koch, W. J. (1998). Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. Am J Physiol Heart Circ Physiol, 275(4), H1298–H1306. https://doi.org/10.1152/ajpheart.1998.275.4.H1298
Iaccarino, Guido, Howard A. Rockman, Kyle F. Shotwell, Eric D. Tomhave, and Walter J. Koch. “Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs.Am J Physiol Heart Circ Physiol 275, no. 4 (October 1, 1998): H1298–1306. https://doi.org/10.1152/ajpheart.1998.275.4.H1298.
Iaccarino G, Rockman HA, Shotwell KF, Tomhave ED, Koch WJ. Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. Am J Physiol Heart Circ Physiol. 1998 Oct 1;275(4):H1298–306.
Iaccarino, Guido, et al. “Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs.Am J Physiol Heart Circ Physiol, vol. 275, no. 4, Oct. 1998, pp. H1298–306. Pubmed, doi:10.1152/ajpheart.1998.275.4.H1298.
Iaccarino G, Rockman HA, Shotwell KF, Tomhave ED, Koch WJ. Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. Am J Physiol Heart Circ Physiol. 1998 Oct 1;275(4):H1298–H1306.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

October 1, 1998

Volume

275

Issue

4

Start / End Page

H1298 / H1306

Location

United States

Related Subject Headings

  • Signal Transduction
  • Rhodopsin
  • Reference Values
  • Receptors, Thrombin
  • Receptors, Adrenergic, beta
  • Receptor Protein-Tyrosine Kinases
  • Radioligand Assay
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Peptide Fragments