Desensitization of adenylate cyclase responses following exposure to IP prostanoid receptor agonists

Krane, Anke; MacDermot, John; Keen, Mary

doi:10.1016/0006-2952(94)90405-7

Cited by 23 publications

(8 citation statements)

References 17 publications

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“…Isoproterenol was purchased from Sigma. [ 3 H]IP 3 (20 -40 Ci/ mmol) and [ 3 H]cAMP (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Ci/mmol) were purchased from American Radiolabeled Chemicals Inc. Polyvinylidene difluoride (PVDF) filters, Taq DNA polymerase, the chemiluminescence Western blotting kit, and rat monoclonal 3F10 anti-hemagglutinin (HA) peroxidase-conjugated antibody were purchased from Roche Molecular Biochemicals. Oligonucleotides were synthesized by Genosys Biotechnologies.…”

Section: Methodsmentioning

confidence: 99%

“…Whereas isoprenylation of mouse (m) IP is not required for ligand binding, it is absolutely required for its activation of adenylyl cyclase and for its efficient coupling to PLC (12,13). In addition, a number of studies have confirmed that the IP undergoes rapid agonistinduced receptor phosphorylation, internalization/sequestration, and down-regulation in human platelets and other cell types (10,(17)(18)(19)(20).…”

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confidence: 99%

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Protein Kinase A-mediated Phosphorylation of Serine 357 of the Mouse Prostacyclin Receptor Regulates Its Coupling to Gs-, to Gi-, and to Gq-coupled Effector Signaling

Lawler

Miggin

Kinsella

2001

Journal of Biological Chemistry

113

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Protein Kinase A-mediated Phosphorylation of Serine 357 of the Mouse Prostacyclin Receptor Regulates Its Coupling to Gs-, to Gi-, and to Gq-coupled Effector Signaling

Lawler

Miggin

Kinsella

2001

Journal of Biological Chemistry

113

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“…A number of independent studies have established that the prostacyclin receptor (IP) undergoes agonist-induced phosphorylation, desensitization and down-regulation in human platelets and other cell types, providing an important mechanism of fine-tuning the cellular responses to prostacyclin in vivo [30][31][32][33][34]. While the hIP undergoes agonist-induced protein kinase (PK)C phosphorylation within its C-tail domain, desensitizing its signaling [33], its internalization is entirely independent of both PKC and the classic GRK/β-arrestin-mediated mechanism [34].…”

Section: Introductionmentioning

confidence: 99%

Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase

Wikström

Reid

Hill

et al. 2008

Cellular Signalling

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Running Title: Role of Rab11 and Rab4 in recycling of the human prostacyclin receptor.Key Words: human prostacyclin receptor, internalization, Rab11a, Rab4a, yeast-two-hybrid, GPCR. -2 - ABSTRACTThe human prostacyclin receptor (hIP) undergoes agonist-induced internalization but the mechanisms regulating its intracellular trafficking and/or recycling to the plasma membrane are poorly understood.Herein, we conducted a yeast-two-hybrid screen to identify proteins interacting with the carboxyl terminal (C)-tail domain of the hIP and discovered a novel interaction with Rab11a. This interaction was confirmed by co-immunoprecipitations in mammalian HEK293 and was augmented by cicaproststimulation. The hIP co-localized to Rab11-containing recycling endosomes in both HEK293 and endothelial EA.hy 926 cells in a time-dependent manner following cicaprost-stimulation. Moreover, over-expression of Rab11a significantly increased recycling of the hIP, while the dominant negative Rab11S25N impaired that recycling. Conversely, while the hIP co-localized to Rab4-positive endosomes in response to cicaprost, ectopic expression of Rab4a did not substantially affect overall recycling nor did Rab4a directly interact with the hIP. The specific interaction between the hIP and Rab11a was dependent on a 22 amino acid (Val 299 -Gln 320 ) sequence within its C-tail domain and was independent of isoprenylation of the hIP. This study elucidates a critical role for Rab11a in regulating trafficking of the hIP and has identified a novel Rab11 binding-domain (RBD) within its C-tail domain that is both necessary and sufficient to mediate interaction with Rab11a.

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“…2). Also, unlike forskolin, the effects of prostanoids on adenylyl cyclase activity are subject to ligand stability (Thompson et al, 1973;Lucas et al, 1986), receptor desensitization (Krane et al, 1994), and modulation of GTP-binding protein association (Adie et al, 1992;Adie and Milligan, 1994). Based on these significant differences in the mechanism of action, the acute and chronic responses of Schwann cells to a receptormediated elevation in cyclic AMP will likely be different from that of forskolin.…”

Section: Discussionmentioning

confidence: 99%

Schwann cells express IP prostanoid receptors coupled to an elevation in intracellular cyclic AMP

Muja

Nelson

DeVries

2007

J of Neuroscience Research

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We have shown previously that prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) are each produced in an explant model of peripheral nerve injury. We report that IP prostanoid receptor mRNA and protein are present in primary rat Schwann cells. IP prostanoid receptor stimulation using prostacyclin produced an elevation in intracellular cyclic AMP concentration ([cAMP](i)) in primary Schwann cells. Peak [cAMP](i) was observed between 5-15 min of stimulation followed by a gradual recovery toward basal level. Phosphorylation of cyclic AMP-response element binding protein (CREB) on Ser(133) was also detected after IP prostanoid receptor stimulation and CREB phosphorylation was inhibited completely by the protein kinase A inhibitor, H-89. Intracellular calcium levels were not affected by IP prostanoid receptor stimulation. Unlike forskolin, IP prostanoid receptor stimulation did not significantly augment Schwann cell proliferation in response to growth factor treatment. However, IP prostanoid receptor stimulation increased the number of Schwann cells that were able to generate a calcium transient in response to P2 purinergic receptor activation. These findings suggest that signaling via the IP prostanoid receptor may by relevant to Schwann cell biology in vivo.

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Desensitization of adenylate cyclase responses following exposure to IP prostanoid receptor agonists

Cited by 23 publications

References 17 publications

Protein Kinase A-mediated Phosphorylation of Serine 357 of the Mouse Prostacyclin Receptor Regulates Its Coupling to Gs-, to Gi-, and to Gq-coupled Effector Signaling

Protein Kinase A-mediated Phosphorylation of Serine 357 of the Mouse Prostacyclin Receptor Regulates Its Coupling to Gs-, to Gi-, and to Gq-coupled Effector Signaling

Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase

Schwann cells express IP prostanoid receptors coupled to an elevation in intracellular cyclic AMP

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