Cloning, Pharmacology, and Tissue Distribution of G-Protein-Coupled Receptor GPR105 (KIAA0001) Rodent Orthologs

Freeman, Katie B.; Tsui, Ping; Moore, Darren J.; Emson, Piers C.; Vawter, Lisa; Naheed, Sajda; Lane, Pamela; Bawagan, Hinayana; Herrity, Nicole C.; Murphy, Kay; Sarau, Henry M.; Ames, Robert S.; Wilson, Shelagh; Livi, George P.; Chambers, Jon

doi:10.1006/geno.2001.6662

Cited by 72 publications

(69 citation statements)

References 17 publications

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“…5). Collectively, these results strongly suggest that UDP-glucose released into CF-like diseased airways acts as a pro-inflammatory mediator, via stimulation of the P2Y 14 R. P2Y 14 R mRNA is expressed in human [45] and murine [46] lungs [17,46] and inflammatory cells [17][18][19][20][21], but the identity of the cell type(s) potentially sensing UDP-glucose in airway surface liquids is not known. We observed no P2Y 14 R mRNA amplification in well-differentiated primary cultures of bronchial epithelial cells (data not shown).…”

Section: Discussionmentioning

confidence: 96%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y 14 receptors (P2Y 14 R). However, the physiological/pathophysiological consequences of UDPsugar release are incompletely defined. Here, we report that UDP-glucose levels are abnormally elevated in lung secretions from patients with cystic fibrosis (CF) as well as in a mouse model of CF-like disease, the βENaC transgenic (Tg) mouse. Instillation of UDP-glucose into wild-type mouse tracheas resulted in enhanced neutrophil lung recruitment, and this effect was nearly abolished when UDP-glucose was coinstilled with the P2Y 14 R antagonist PPTN [4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl-2-naphthoic acid]. Importantly, administration of PPTN to βENaC-Tg mice reduced neutrophil lung inflammation. These results suggest that UDP-glucose released into the airways acts as a local mediator of neutrophil inflammation.

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Section: Discussionmentioning

confidence: 96%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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“…UDP-N-acetylglucosamine, and all these molecules exhibited potencies in the 0.1-1.0 mM range of concentrations. One potential caveat from this and additional early studies was that they were accomplished using overexpressed G-protein a-subunits, either with Ga 16 , which mediates coupling of essentially all GPCR to phospholipase C-b isozymes, or with the engineered protein, Ga q/i , which selectively couples G i -linked GPCR to activation of phospholipase C-b (Chambers et al, 2000;Freeman et al, 2001;Lazarowski et al, 2003;Fricks et al, 2008). Nonetheless, results from work studying the agonist selectivity of the P2Y 14 R in cell systems in which it coupled through native G i heterotrimers to promote inhibition of adenylyl cyclase confirmed the nucleotide sugar selectivity established by Chambers and coworkers; that is, UDP-glucose is the most potent agonist, but the activities of other nucleotide sugars are within an order of magnitude .…”

Section: Mechanisms Of Release and Metabolism Of Nucleotide Sugarsmentioning

confidence: 99%

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

Lazarowski

Harden

2015

Mol Pharmacol

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UDP-sugars, which are indispensable for protein glycosylation reactions in cellular secretory pathways, also act as important extracellular signaling molecules. We discuss here the broadly expressed P2Y 14 receptor, a G-protein-coupled receptor targeted by UDP sugars, and the increasingly diverse set of physiologic responses discovered recently functioning downstream of this receptor in many epithelia as well as in immune, inflammatory, and other cells.

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“…Accordingly, it has been shown that reducing the cellular level of UDP-GlcNAc to 5% of the normal level did not affect the synthesis or secretion of N-linked glycoproteins (58). Moreover, a G protein-coupled specific cell surface receptor for UDP-Glc, P2Y 14 , was recently identified (59,60), and the release of small amounts of UDP-Glc from a variety of cultured cells into the medium was demonstrated (61). UDP-Glc was postulated as a novel autocrine and paracrine signaling molecule, although the physiological processes regulated by its widely distributed receptor remain to be clarified.…”

Section: Fig 6 a Cellular Udp-glc Deficiency Does Not Cause Xbp-1 Amentioning

confidence: 99%

A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements

Flores-Dı́az

Higuita

Florin

et al. 2004

Journal of Biological Chemistry

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A low level of UDP-Glc occurs in cells exposed to hypoxia or glucose starvation. This work reveals that a 65% reduction in the cellular UDP-Glc level causes upregulation of the mitochondrial chaperone GRP75 and the endoplasmic reticulum (ER) resident chaperones GRP58, ERp72, GRP78, GRP94, GRP170, and calreticulin. Conditions that cause misfolding of proteins within the ER activate the transcription factors ATF6␣/␤ and induce translation of the transcription factors XBP-1/ TREB5 and ATF4/CREB2. These transcription factors induce the overexpression of ER chaperones and CHOP/ GADD153. However, the 65% decrease in the cellular UDP-Glc level does not cause activation of ATF6␣, splicing of XBP-1/TREB5, induction of ATF4/CREB2, or expression of CHOP/GADD153. The activity of the promoters of the ER chaperones is increased in UDP-Glcdeficient cells, but the activity of the CHOP/GADD153 promoter is not affected, in comparison with their respective activities in cells having compensated for the UDP-Glc deficiency. The results demonstrate that the unfolded protein response remains functionally intact in cells with a 65% decrease in the cellular UDP-Glc level and provide evidence that this decrease is a stress signal in mammalian cells, which triggers the coordinate overexpression of mitochondrial and ER chaperones, independently of the ER stress elements.

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Cloning, Pharmacology, and Tissue Distribution of G-Protein-Coupled Receptor GPR105 (KIAA0001) Rodent Orthologs

Cited by 72 publications

References 17 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements

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Cloning, Pharmacology, and Tissue Distribution of G-Protein-Coupled Receptor GPR105 (KIAA0001) Rodent Orthologs

Cited by 72 publications

References 17 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation

A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements

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UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation