Homologous desensitization of signalling by the beta (β) isoform of the human thromboxane A2 receptor

Kelley-Hickie, Leanne P.; Kinsella, B. Thérèse

doi:10.1016/j.bbalip.2006.07.012

Cited by 27 publications

(35 citation statements)

References 55 publications

(80 reference statements)

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“…The cellular responses to TXA 2 are subject to regulation by both agonist-dependent homologous desensitization (24,25) and by cross-talk with other signaling systems (23,27,29), which mainly occur through direct phosphorylation of the TP␣ and/or TP␤ isoforms themselves. For example, both TP␣ and TP␤ undergo PKC phosphorylation within their IC (e.g.…”

mentioning

confidence: 99%

“…TP␣ and TP␤ also undergo entirely distinct mechanisms of both agonist-induced (homologous) desensitization (24,25) and heterologous desensitization or cross-talk/regulation by other signaling systems such as prostacyclin and nitric oxide (23, 26 -29). Such differences in desensitization of TP␣ and TP␤ signaling occur because of differences in their phosphorylation, occurring mainly within their unique C-tail domains, by the second messenger-regulated protein kinases, including by protein kinase (PK) C, PKA, PKG, and/or by GPCR-regulated kinases 1/2 (23)(24)(25)(26)(27)29).…”

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confidence: 99%

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Identification of an Interaction between the TPα and TPβ Isoforms of the Human Thromboxane A2 Receptor with Protein Kinase C-related Kinase (PRK) 1

Turner¹,

Kavanagh²,

Mulvaney

et al. 2011

Journal of Biological Chemistry

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confidence: 99%

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confidence: 99%

Identification of an Interaction between the TPα and TPβ Isoforms of the Human Thromboxane A2 Receptor with Protein Kinase C-related Kinase (PRK) 1

Turner¹,

Kavanagh²,

Mulvaney

et al. 2011

Journal of Biological Chemistry

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“…For example, harrestin 2 binds to and down-regulates the transforming growth factor h-dependent inhibition of cell proliferation (18). Recent data showed that TP-h interacts with h-arrestin 2 (19). We determined that bladder cancer cell lines express high levels of h-arrestin 2 (data not shown).…”

Section: Cancer Researchmentioning

confidence: 99%

Novel Role of Thromboxane Receptors β Isoform in Bladder Cancer Pathogenesis

et al. 2008

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These studies were undertaken to determine the potential role of thromboxane receptors (TP) in bladder cancer. The data reported herein show that expression of the TP-B receptor protein is increased in tissue obtained from patients with bladder cancer and associated with a significantly poorer prognosis (P < 0.005). Bladder cancer cell lines express the TP-B isoform, unlike immortalized nontransformed urothelial cells (SV-HUC) that express only the TP-A isoform. TP-B receptor expression, but not TP-A, promoted cell proliferation, migration, and invasion in vitro, and also resulted in malignant transformation of SV-HUC cells in vivo. Agonist-mediated phosphorylation of extracellular signal-regulated kinase and FAK was dependent on the expression of TP-B. Furthermore, TP-B mediated multiple biological effects by signaling through either G-protein A subunit 12 or B-arrestin 2. Treatment of mice with the TP receptor antagonist GR32191, alone or in combination with cisplatin, significantly delayed tumor onset and prolonged survival of mice transplanted with TCC-SUP bladder cancer cells compared with vehicle or cisplatin alone. These results support the model that the TP-B receptor isoform plays a unique role in bladder cancer progression and its expression may have predictive value and provide a novel therapeutic target. [Cancer Res 2008;68(11):4097-104]

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“…homologous (15,16) and heterologous (17)(18)(19) desensitization to differentially regulate their intracellular signalling. Most notably, signalling by TPα, but not by TPβ, is completely desensitized/inhibited by the counter-regulatory anti-platelet and vasodilatory agents prostacyclin/prostaglandin I 2 and nitric oxide, which is mediated by direct protein kinase (PK) A and PKG phosphorylation of TPα at Ser 329 and Ser 331 , respectively, the very first residues within its unique carboxyl-terminal tail domain of TPα and divergent from those of TPβ (13,18).…”

Section: Figurementioning

confidence: 99%

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

Kinsella

2016

Wilms Tumor

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Copyright: The Author.Licence: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the author and the publisher are explicitly identified and properly acknowledged as the original source. AbstractThe prostanoid thromboxane (TX)A 2 plays a fundamental role in vascular haemostasis and, more recently, is increasingly implicated in various neoplasms including in prostate, breast and bladder cancers, among others. In humans, TXA 2 signals through the TPα and TPβ isoforms of the T prostanoid receptor (TP), two structurally related receptors that display both common, over-lapping but also distinct, isoform-specific physiologic roles. Consistent with this, while TPα and TPβ are encoded by the same gene, the TBXA2R, they are Kinsella 164 differentially expressed due to their transcriptional regulation by distinct promoters where promoter (Prm) 1 regulates TPα expression and Prm3 regulates TPβ. While the clinical evidence for the role of the TXA 2 -TP axis in neoplastic progression is increasing, few studies to date have investigated the role of the individual TPα/TPβ isoforms in human cancer or indeed in most other diseases in which the TXA 2 -TP axis is implicated. Focusing on TPα, this review details the current understanding of the factors regulating its expression and transcriptional regulation through Prm1, including in prostate and breast cancers. Emphasis is placed on the trans-acting transcriptional regulators that bind to cis-elements within the core and upstream regulatory regions of Prm1 under basal conditions and in response to cellular differentiation. A particular focus is placed on the role of the tumour suppressor Wilms' tumour 1 in the regulation of TPα expression through Prm1 in megakaryoblastic cells of vascular origin and in prostate and breast carcinoma cells. Collectively, this review details current knowledge of the factors determining regulation of the TXA 2 -TPα axis and thereby provides a genetic basis for understanding the role of TXA 2 in the progression of certain human cancers.

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Homologous desensitization of signalling by the beta (β) isoform of the human thromboxane A2 receptor

Cited by 27 publications

References 55 publications

Identification of an Interaction between the TPα and TPβ Isoforms of the Human Thromboxane A2 Receptor with Protein Kinase C-related Kinase (PRK) 1

Identification of an Interaction between the TPα and TPβ Isoforms of the Human Thromboxane A2 Receptor with Protein Kinase C-related Kinase (PRK) 1

Novel Role of Thromboxane Receptors β Isoform in Bladder Cancer Pathogenesis

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

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