Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase.

Publication ,  Journal Article
Inglese, J; Luttrell, LM; Iñiguez-Lluhi, JA; Touhara, K; Koch, WJ; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
April 26, 1994

The beta-adrenergic receptor kinase (beta ARK) phosphorylates its membrane-associated receptor substrates, such as the beta-adrenergic receptor, triggering events leading to receptor desensitization. beta ARK activity is markedly stimulated by the isoprenylated beta gamma subunit complex of heterotrimeric guanine nucleotide-binding proteins (G beta gamma), which translocates the kinase to the plasma membrane and thereby targets it to its receptor substrate. The amino-terminal two-thirds of beta ARK1 composes the receptor recognition and catalytic domains, while the carboxyl third contains the G beta gamma binding sequences, the targeting domain. We prepared this domain as a recombinant His6 fusion protein from Escherichia coli and found that it had both independent secondary structure and functional activity. We demonstrated the inhibitory properties of this domain against G beta gamma activation of type II adenylyl cyclase both in a reconstituted system utilizing Sf9 insect cell membranes and in a permeabilized 293 human embryonic kidney cell system. Gi alpha-mediated inhibition of adenylyl cyclase was not affected. These data suggest that this His6 fusion protein derived from the carboxyl terminus of beta ARK1 provides a specific probe for defining G beta gamma-mediated processes and for studying the structural features of a G beta gamma-binding domain.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 26, 1994

Volume

91

Issue

9

Start / End Page

3637 / 3641

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Virulence Factors, Bordetella
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta
  • Rats
  • Protein Structure, Secondary
  • Molecular Sequence Data
  • In Vitro Techniques
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Inglese, J., Luttrell, L. M., Iñiguez-Lluhi, J. A., Touhara, K., Koch, W. J., & Lefkowitz, R. J. (1994). Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase. Proc Natl Acad Sci U S A, 91(9), 3637–3641. https://doi.org/10.1073/pnas.91.9.3637
Inglese, J., L. M. Luttrell, J. A. Iñiguez-Lluhi, K. Touhara, W. J. Koch, and R. J. Lefkowitz. “Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase.Proc Natl Acad Sci U S A 91, no. 9 (April 26, 1994): 3637–41. https://doi.org/10.1073/pnas.91.9.3637.
Inglese J, Luttrell LM, Iñiguez-Lluhi JA, Touhara K, Koch WJ, Lefkowitz RJ. Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3637–41.
Inglese, J., et al. “Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase.Proc Natl Acad Sci U S A, vol. 91, no. 9, Apr. 1994, pp. 3637–41. Pubmed, doi:10.1073/pnas.91.9.3637.
Inglese J, Luttrell LM, Iñiguez-Lluhi JA, Touhara K, Koch WJ, Lefkowitz RJ. Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3637–3641.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 26, 1994

Volume

91

Issue

9

Start / End Page

3637 / 3641

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Virulence Factors, Bordetella
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta
  • Rats
  • Protein Structure, Secondary
  • Molecular Sequence Data
  • In Vitro Techniques
  • Humans