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The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2.

Publication ,  Journal Article
Kwatra, MM; Schwinn, DA; Schreurs, J; Blank, JL; Kim, CM; Benovic, JL; Krause, JE; Caron, MG; Lefkowitz, RJ
Published in: J Biol Chem
May 5, 1993

The agonist-occupied forms of several G-protein-coupled receptors that modulate the activity of adenylycyclase via Gs (e.g. beta 2-adrenergic) or Gi (e.g. alpha 2-adrenergic and cardiac muscarinic) are phosphorylated by beta-adrenergic receptor kinases (beta ARK 1 and beta ARK 2). beta ARK-catalyzed phosphorylation of these receptors appears to correlate with their agonist-induced desensitization. The possibility that beta ARK isozymes may also be involved in the desensitization of other G-protein-coupled receptors such as those mediating phosphoinositide (PI) hydrolysis was tested by determining the phosphorylation of the substance P receptor (SPR), which is coupled to PI hydrolysis in numerous tissues. Rat SPR was expressed in Sf9 cells, partially purified, and reconstituted in phospholipid vesicles. The reconstituted SPR bound the SPR agonist substance P, 125I-labeled with Bolton-Hunter reagent, with low affinity. However, addition of purified Gq/11 to the reconstituted SPR resulted in the conversion of all the receptors to a high affinity state, suggesting that SPR couples to Gq/11. Phosphorylation of the reconstituted SPR with purified beta ARK 1 or 2 in the absence and presence of substance P (SP) was then studied. In the presence of 100 microM SP, both kinases promoted phosphorylation of the receptor to a stoichiometry of 9 +/- 2 mol of phosphate/mol of receptor. However, no phosphorylation of the receptor could be detected in the absence of agonist. Agonist-induced phosphorylation of the receptor was blocked by coincubation with the SPR antagonist spantide. These results show that beta ARK isozymes may regulate the function of both adenylylcyclase as well as PI-coupled receptors, and suggest a role for beta ARK isozymes in SPR signal transduction.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 5, 1993

Volume

268

Issue

13

Start / End Page

9161 / 9164

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Substance P
  • Recombinant Proteins
  • Receptors, Neurotransmitter
  • Receptors, Neurokinin-1
  • Rats
  • Protein Kinases
  • Phosphorylation
  • Moths
 

Citation

APA
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Kwatra, M. M., Schwinn, D. A., Schreurs, J., Blank, J. L., Kim, C. M., Benovic, J. L., … Lefkowitz, R. J. (1993). The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2. J Biol Chem, 268(13), 9161–9164.
Kwatra, M. M., D. A. Schwinn, J. Schreurs, J. L. Blank, C. M. Kim, J. L. Benovic, J. E. Krause, M. G. Caron, and R. J. Lefkowitz. “The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2.J Biol Chem 268, no. 13 (May 5, 1993): 9161–64.
Kwatra MM, Schwinn DA, Schreurs J, Blank JL, Kim CM, Benovic JL, et al. The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2. J Biol Chem. 1993 May 5;268(13):9161–4.
Kwatra, M. M., et al. “The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2.J Biol Chem, vol. 268, no. 13, May 1993, pp. 9161–64.
Kwatra MM, Schwinn DA, Schreurs J, Blank JL, Kim CM, Benovic JL, Krause JE, Caron MG, Lefkowitz RJ. The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2. J Biol Chem. 1993 May 5;268(13):9161–9164.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 5, 1993

Volume

268

Issue

13

Start / End Page

9161 / 9164

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Substance P
  • Recombinant Proteins
  • Receptors, Neurotransmitter
  • Receptors, Neurokinin-1
  • Rats
  • Protein Kinases
  • Phosphorylation
  • Moths