Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8

Sergey Ryzhov, Rinat Zaynagetdinov, Anna E. Goldstein, Anton Matafonov, Italo Biaggioni, Igor Feoktistov

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In human mast cells and microvascular endothelial cells, the A2B adenosine receptor controls at least three independent signaling pathways, i.e., Gs-mediated stimulation of adenylate cyclase, Gq-mediated stimulation of phospholipase Cβ, and Gs/Gq-independent upregulation of IL-8. Functional analysis of cells transfected with full-length and truncated receptor constructs revealed that the A2B receptor C-terminus is important for coupling to Gs and Gq proteins. Removal of the entire cytoplasmic portion in the A2B receptor C-terminus rendered it incapable of stimulating adenylate cyclase and phospholipase Cβ. Conversely, removal of the distal 16 amino acids facilitated signal transduction from the receptor to the downstream Gs but not Gq proteins. However, the A2B receptor C-terminus is not essential for upregulation of IL-8. Analysis of chimeric A2A/A2B receptors demonstrated that only chimeras containing the third intracellular loop of the A2B receptor mediated agonist-dependent IL-8 reporter stimulation, suggesting that this domain is important for upregulation of IL-8.

Original languageEnglish
Pages (from-to)289-298
Number of pages10
JournalPurinergic Signalling
Volume5
Issue number3
DOIs
Publication statusPublished - 7 Jan 2009
Externally publishedYes

Fingerprint

Adenosine A2B Receptors
Type C Phospholipases
Interleukin-8
Adenylyl Cyclases
Gq-G11 GTP-Binding Protein alpha Subunits
Up-Regulation
Mast Cells
Signal Transduction
Endothelial Cells
Amino Acids

Keywords

  • Adenosine
  • Adenylate cyclase
  • GTP-binding proteins
  • Interleukin-8
  • Purinergic receptors P1
  • Type C phospholipases

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8. / Ryzhov, Sergey; Zaynagetdinov, Rinat; Goldstein, Anna E.; Matafonov, Anton; Biaggioni, Italo; Feoktistov, Igor.

In: Purinergic Signalling, Vol. 5, No. 3, 07.01.2009, p. 289-298.

Research output: Contribution to journalArticle

Ryzhov, Sergey ; Zaynagetdinov, Rinat ; Goldstein, Anna E. ; Matafonov, Anton ; Biaggioni, Italo ; Feoktistov, Igor. / Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8. In: Purinergic Signalling. 2009 ; Vol. 5, No. 3. pp. 289-298.
@article{119f9086b954451d8de98034380af912,
title = "Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8",
abstract = "In human mast cells and microvascular endothelial cells, the A2B adenosine receptor controls at least three independent signaling pathways, i.e., Gs-mediated stimulation of adenylate cyclase, Gq-mediated stimulation of phospholipase Cβ, and Gs/Gq-independent upregulation of IL-8. Functional analysis of cells transfected with full-length and truncated receptor constructs revealed that the A2B receptor C-terminus is important for coupling to Gs and Gq proteins. Removal of the entire cytoplasmic portion in the A2B receptor C-terminus rendered it incapable of stimulating adenylate cyclase and phospholipase Cβ. Conversely, removal of the distal 16 amino acids facilitated signal transduction from the receptor to the downstream Gs but not Gq proteins. However, the A2B receptor C-terminus is not essential for upregulation of IL-8. Analysis of chimeric A2A/A2B receptors demonstrated that only chimeras containing the third intracellular loop of the A2B receptor mediated agonist-dependent IL-8 reporter stimulation, suggesting that this domain is important for upregulation of IL-8.",
keywords = "Adenosine, Adenylate cyclase, GTP-binding proteins, Interleukin-8, Purinergic receptors P1, Type C phospholipases",
author = "Sergey Ryzhov and Rinat Zaynagetdinov and Goldstein, {Anna E.} and Anton Matafonov and Italo Biaggioni and Igor Feoktistov",
year = "2009",
month = "1",
day = "7",
doi = "10.1007/s11302-008-9129-8",
language = "English",
volume = "5",
pages = "289--298",
journal = "Purinergic Signalling",
issn = "1573-9538",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8

AU - Ryzhov, Sergey

AU - Zaynagetdinov, Rinat

AU - Goldstein, Anna E.

AU - Matafonov, Anton

AU - Biaggioni, Italo

AU - Feoktistov, Igor

PY - 2009/1/7

Y1 - 2009/1/7

N2 - In human mast cells and microvascular endothelial cells, the A2B adenosine receptor controls at least three independent signaling pathways, i.e., Gs-mediated stimulation of adenylate cyclase, Gq-mediated stimulation of phospholipase Cβ, and Gs/Gq-independent upregulation of IL-8. Functional analysis of cells transfected with full-length and truncated receptor constructs revealed that the A2B receptor C-terminus is important for coupling to Gs and Gq proteins. Removal of the entire cytoplasmic portion in the A2B receptor C-terminus rendered it incapable of stimulating adenylate cyclase and phospholipase Cβ. Conversely, removal of the distal 16 amino acids facilitated signal transduction from the receptor to the downstream Gs but not Gq proteins. However, the A2B receptor C-terminus is not essential for upregulation of IL-8. Analysis of chimeric A2A/A2B receptors demonstrated that only chimeras containing the third intracellular loop of the A2B receptor mediated agonist-dependent IL-8 reporter stimulation, suggesting that this domain is important for upregulation of IL-8.

AB - In human mast cells and microvascular endothelial cells, the A2B adenosine receptor controls at least three independent signaling pathways, i.e., Gs-mediated stimulation of adenylate cyclase, Gq-mediated stimulation of phospholipase Cβ, and Gs/Gq-independent upregulation of IL-8. Functional analysis of cells transfected with full-length and truncated receptor constructs revealed that the A2B receptor C-terminus is important for coupling to Gs and Gq proteins. Removal of the entire cytoplasmic portion in the A2B receptor C-terminus rendered it incapable of stimulating adenylate cyclase and phospholipase Cβ. Conversely, removal of the distal 16 amino acids facilitated signal transduction from the receptor to the downstream Gs but not Gq proteins. However, the A2B receptor C-terminus is not essential for upregulation of IL-8. Analysis of chimeric A2A/A2B receptors demonstrated that only chimeras containing the third intracellular loop of the A2B receptor mediated agonist-dependent IL-8 reporter stimulation, suggesting that this domain is important for upregulation of IL-8.

KW - Adenosine

KW - Adenylate cyclase

KW - GTP-binding proteins

KW - Interleukin-8

KW - Purinergic receptors P1

KW - Type C phospholipases

UR - http://www.scopus.com/inward/record.url?scp=68349144415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68349144415&partnerID=8YFLogxK

U2 - 10.1007/s11302-008-9129-8

DO - 10.1007/s11302-008-9129-8

M3 - Article

VL - 5

SP - 289

EP - 298

JO - Purinergic Signalling

JF - Purinergic Signalling

SN - 1573-9538

IS - 3

ER -