The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2 - PubMed (original) (raw)
. 1993 May 5;268(13):9161-4.
Affiliations
- PMID: 7683643
Free article
The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2
M M Kwatra et al. J Biol Chem. 1993.
Free article
Abstract
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.
Similar articles
- Phosphorylation and desensitization of human m2 muscarinic cholinergic receptors by two isoforms of the beta-adrenergic receptor kinase.
Richardson RM, Kim C, Benovic JL, Hosey MM. Richardson RM, et al. J Biol Chem. 1993 Jun 25;268(18):13650-6. J Biol Chem. 1993. PMID: 8514797 - Mechanism of beta-adrenergic receptor kinase activation by G proteins.
Kim CM, Dion SB, Benovic JL. Kim CM, et al. J Biol Chem. 1993 Jul 25;268(21):15412-8. J Biol Chem. 1993. PMID: 8393441 - [Regulation of G protein-coupled receptor kinase activity].
Haga T, Haga K, Kameyama K, Nakata H. Haga T, et al. Nihon Yakurigaku Zasshi. 1994 Sep;104(3):207-16. doi: 10.1254/fpj.104.207. Nihon Yakurigaku Zasshi. 1994. PMID: 7959413 Review. Japanese. - G-protein-coupled receptor kinases.
Palczewski K, Benovic JL. Palczewski K, et al. Trends Biochem Sci. 1991 Oct;16(10):387-91. doi: 10.1016/0968-0004(91)90157-q. Trends Biochem Sci. 1991. PMID: 1664548 Review.
Cited by
- Quantitative comparisons of muscarinic and bradykinin receptor-mediated Ins (1,4,5)P3 accumulation and Ca2+ signalling in human neuroblastoma cells.
Willars GB, Nahorski SR. Willars GB, et al. Br J Pharmacol. 1995 Mar;114(6):1133-42. doi: 10.1111/j.1476-5381.1995.tb13325.x. Br J Pharmacol. 1995. PMID: 7620702 Free PMC article. - The evolving impact of g protein-coupled receptor kinases in cardiac health and disease.
Sato PY, Chuprun JK, Schwartz M, Koch WJ. Sato PY, et al. Physiol Rev. 2015 Apr;95(2):377-404. doi: 10.1152/physrev.00015.2014. Physiol Rev. 2015. PMID: 25834229 Free PMC article. Review. - Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo.
Mantyh PW, Allen CJ, Ghilardi JR, Rogers SD, Mantyh CR, Liu H, Basbaum AI, Vigna SR, Maggio JE. Mantyh PW, et al. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2622-6. doi: 10.1073/pnas.92.7.2622. Proc Natl Acad Sci U S A. 1995. PMID: 7535928 Free PMC article. - Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism.
Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F. Meshki J, et al. J Biol Chem. 2009 Apr 3;284(14):9280-9. doi: 10.1074/jbc.M808825200. Epub 2009 Jan 28. J Biol Chem. 2009. PMID: 19179340 Free PMC article. - Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins.
Fields TA, Casey PJ. Fields TA, et al. Biochem J. 1997 Feb 1;321 ( Pt 3)(Pt 3):561-71. doi: 10.1042/bj3210561. Biochem J. 1997. PMID: 9032437 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous