Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2004 Aug 15;382Pt 1:101-10. doi: 10.1042/BJ20031910.
Show Gene links
Show Anatomy links
G-protein-coupled receptor regulation of P2X1 receptors does not involve direct channel phosphorylation.
Vial C
,
Tobin AB
,
Evans RJ
.
???displayArticle.abstract???
P2X1 receptors for ATP are ligand-gated cation channels, which mediate smooth muscle contraction, contribute to blood clotting and are co-expressed with a range of GPCRs (G-protein-coupled receptors). Stimulation of Galpha(q)-coupled mGluR1alpha (metabotropic glutamate receptor 1alpha), P2Y1 or P2Y2 receptors co-expressed with P2X(1) receptors in Xenopus oocytes evoked calcium-activated chloride currents (I(ClCa)) and potentiated subsequent P2X1-receptor-mediated currents by up to 250%. The mGluR1alpha-receptor-mediated effects were blocked by the phospholipase C inhibitor U-73122. Potentiation was mimicked by treatment with the phor-bol ester PMA. P2X receptors have a conserved intracellular PKC (protein kinase C) site; however, GPCR- and PMA-mediated potentiation was still observed with point mutants in which this site was disrupted. Similarly, the potentiation by GPCRs or PMA was unaffected by chelating the intracellular calcium rise with BAPTA/AM [bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis-(acetoxymethyl ester)] or the PKC inhibitors Ro-32-0432 and bisindolylmaleimide I, suggesting that the regulation does not involve a calcium-sensitive form of PKC. However, both GPCR and PMA potentiation were blocked by the kinase inhibitor staurosporine. Potentiation by phorbol esters was recorded in HEK-293 cells expressing P2X1 receptors, and radiolabelling of phosphorylated proteins in these cells demonstrated that P2X1 receptors are basally phosphorylated and that this level of phosphorylation is unaffected by phorbol ester treatment. This demonstrates that P2X1 regulation does not result directly from phosphorylation of the channel, but more likely by a staurosporine-sensitive phosphorylation of an accessory protein in the P2X1 receptor complex and suggests that in vivo fine-tuning of P2X1 receptors by GPCRs may contribute to cardiovascular control and haemostasis.
Adinolfi,
Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors.
2003, Pubmed
Adinolfi,
Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors.
2003,
Pubmed
Boué-Grabot,
A protein kinase C site highly conserved in P2X subunits controls the desensitization kinetics of P2X(2) ATP-gated channels.
2000,
Pubmed
,
Xenbase
Budd,
Phosphorylation and regulation of a Gq/11-coupled receptor by casein kinase 1alpha.
2000,
Pubmed
Budd,
Phosphorylation of the Gq/11-coupled m3-muscarinic receptor is involved in receptor activation of the ERK-1/2 mitogen-activated protein kinase pathway.
2001,
Pubmed
Burnstock,
The past, present and future of purine nucleotides as signalling molecules.
1997,
Pubmed
Cockayne,
Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.
2000,
Pubmed
Ennion,
P2X(1) receptor subunit contribution to gating revealed by a dominant negative PKC mutant.
2002,
Pubmed
,
Xenbase
Ennion,
The role of positively charged amino acids in ATP recognition by human P2X(1) receptors.
2000,
Pubmed
,
Xenbase
Hechler,
A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo.
2003,
Pubmed
Huang,
Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.
1993,
Pubmed
,
Xenbase
Kunapuli,
Platelet purinergic receptors.
2003,
Pubmed
La,
Endothelin-1 enhances vasoconstrictor responses to exogenously administered and neurogenically released ATP in rabbit isolated perfused arteries.
1993,
Pubmed
Lan,
Protein kinase C modulates NMDA receptor trafficking and gating.
2001,
Pubmed
,
Xenbase
Lan,
Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking.
2001,
Pubmed
,
Xenbase
Lewis,
Lack of run-down of smooth muscle P2X receptor currents recorded with the amphotericin permeabilized patch technique, physiological and pharmacological characterization of the properties of mesenteric artery P2X receptor ion channels.
2000,
Pubmed
Liu,
Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors.
2000,
Pubmed
Liu,
P2X1 receptor currents after disruption of the PKC site and its surroundings by dominant negative mutations in HEK293 cells.
2003,
Pubmed
Lustig,
Expression cloning of an ATP receptor from mouse neuroblastoma cells.
1993,
Pubmed
,
Xenbase
Mahaut-Smith,
ADP is not an agonist at P2X(1) receptors: evidence for separate receptors stimulated by ATP and ADP on human platelets.
2000,
Pubmed
,
Xenbase
Mulryan,
Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.
2000,
Pubmed
North,
Molecular physiology of P2X receptors.
2002,
Pubmed
Paukert,
Inflammatory mediators potentiate ATP-gated channels through the P2X(3) subunit.
2001,
Pubmed
,
Xenbase
Ralevic,
Receptors for purines and pyrimidines.
1998,
Pubmed
Saugstad,
Metabotropic glutamate receptors activate G-protein-coupled inwardly rectifying potassium channels in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Skeberdis,
mGluR1-mediated potentiation of NMDA receptors involves a rise in intracellular calcium and activation of protein kinase C.
2001,
Pubmed
,
Xenbase
Skeberdis,
Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis.
2001,
Pubmed
,
Xenbase
Sneddon,
ATP as a co-transmitter in rat tail artery.
1984,
Pubmed
Souslova,
Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.
2000,
Pubmed
Toth-Zsamboki,
The intracellular tyrosine residues of the ATP-gated P2X(1) ion channel are essential for its function.
2002,
Pubmed
Tsuda,
P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury.
2003,
Pubmed
Valera,
A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP.
1994,
Pubmed
,
Xenbase
Vial,
A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors.
2002,
Pubmed
Vial,
P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries.
2002,
Pubmed
Vial,
P2X receptor expression in mouse urinary bladder and the requirement of P2X(1) receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle.
2000,
Pubmed
Wang,
Regulation of NMDA receptors by tyrosine kinases and phosphatases.
1994,
Pubmed
Webb,
Cloning and functional expression of a brain G-protein-coupled ATP receptor.
1993,
Pubmed
,
Xenbase
Yang,
Divergence and complexities in DAG signaling: looking beyond PKC.
2003,
Pubmed
Zheng,
Protein kinase C potentiation of N-methyl-D-aspartate receptor activity is not mediated by phosphorylation of N-methyl-D-aspartate receptor subunits.
1999,
Pubmed
,
Xenbase