Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation

Watson, Patricia H.; Fraher, L. J.; Natale, Bryony V.; Kisiel, M; Hendy, Geoffrey N.; Hodsman, Anthony B.

doi:10.1016/s8756-3282(99)00264-1

Cited by 60 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After internalization into endosomes, most GPCRs are either recycled to the membrane resulting in resensitization of the cell to the ligand or transferred to lysosomes for degradation (Kobilka, 1992;Mantyh et al, 1995); however, other GPCRs have been shown to enter the nucleus. These include the angiotensin 1 (AT1) receptor (Lu et al, 1998) as well as the closely related apelin and bombesin 2 receptors (Lee et al, 2004) and the parathyroid hormone receptor (Watson et al, 2000). The fact that nuclear localization of NK3 immunoreactivity was increased by the manipulations that induced NK3 internalization, e.g., senktide injection or hypotension, but not by SP injection, supports the hypothesis that nuclear NK3 immunoreactivity reflects ligand-activated NK3 that is translocated from the cell membrane to the nucleus.…”

Section: Discussionmentioning

confidence: 95%

Role of Neurokinin 3 Receptors in Supraoptic Vasopressin and Oxytocin Neurons

Howe

Somponpun²,

Sladek³

2004

J. Neurosci.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 95%

Role of Neurokinin 3 Receptors in Supraoptic Vasopressin and Oxytocin Neurons

Howe

Somponpun²,

Sladek³

2004

J. Neurosci.

View full text Add to dashboard Cite

“…Early studies revealed angiotensin II-binding sites were present in nuclei with angiotensin II-induced transcription of renin and angiotensinogen mRNA (25), and the nuclear localization of the AT 1 receptor was reported to be induced by angiotensin II (26,27). In addition, a family II GPCR, the parathyroid hormone receptor, was observed to localize to the nucleus both in tissues and cultured cells (28), and a recent study observed a family III GPCR, the metabotropic glutamate mGluR5 receptor, in nuclear membranes (29). The prostaglandin EP 1 (30), EP 3 , and EP 4 receptors (31) were observed to have nuclear membrane localization, whereas a recent report (32) described the endo-thelin ETA and ETB receptors to be localized in the nuclear membrane, with ETB receptors present in the interior of the nucleus as well.…”

mentioning

confidence: 99%

Agonist-independent Nuclear Localization of the Apelin, Angiotensin AT1, and Bradykinin B2 Receptors

Lee

Lança

Cheng

et al. 2004

Journal of Biological Chemistry

168

167

View full text Add to dashboard Cite

Signaling of the apelin, angiotensin, and bradykinin peptides is mediated by G protein-coupled receptors related through structure and similarities of physiological function. We report nuclear expression as a characteristic of these receptors, including a nuclear localization for the apelin receptor in brain and cerebellum-derived D283 Med cells and the AT 1 and bradykinin B 2 receptors in HEK-293T cells. Immunocytochemical analyses revealed the apelin receptor with localization in neuronal nuclei in cerebellum and hypothalamus, exhibiting expression in neuronal cytoplasm or in both nuclei and cytoplasm. Confocal microscopy of HEK-293T cells revealed the majority of transfected cells displayed constitutive nuclear localization of AT 1 and B 2 receptors, whereas apelin receptors did not show nuclear localization in these cells. The majority of apelin receptor-transfected cerebellum D283 Med cells showed receptor nuclear expression. Immunoblot analyses of subcellularfractionated D283 Med cells demonstrated endogenous apelin receptor species in nuclear fractions. In addition, an identified nuclear localization signal motif in the third intracellular loop of the apelin receptor was disrupted by a substituted glutamine in place of lysine. This apelin receptor (K242Q) did not exhibit nuclear localization in D283 Med cells. These results demonstrate the following: (i) the apelin receptor exhibits nuclear localization in human brain; (ii) distinct cell-dependent mechanisms for the nuclear transport of apelin, AT 1 , and B 2 receptors; and (iii) the disruption of a nuclear localization signal sequence disrupts the nuclear translocation of the apelin receptor. This discovery of apelin, AT 1 , and B 2 receptors with agonist-independent nuclear translocation suggests major unanticipated roles for these receptors in cell signaling and function.The apelin receptor was discovered as an orphan G proteincoupled receptor (GPCR) 1 known as APJ, sharing highest identity with the angiotensin II AT 1 receptor, although no binding to the receptor was observed with angiotensin II (1). The apelin peptide was subsequently discovered as the endogenous ligand for this receptor (2). At least two isoforms of the apelin peptide are known to exist, apelin-36 and apelin-13, both of which act as agonists of the apelin receptor with distinct pharmacological properties (2-4). The apelinergic system has a widespread pattern of distribution in the brain and periphery as shown for the apelin peptide (3, 5-8) and receptor (6, 9 -11). Apelin has been shown to lower blood pressure (6, 12) and modulate contractility of cardiac tissue and blood vessels (13, 14), pituitary hormone release (15), fluid consumption (6, 15, 16), and cytokine suppression (17) and may have a role as a co-receptor for human immunodeficiency virus entry into cells (18,19). Overall, the apelinergic system is most closely related to the angiotensin and bradykinin systems, as observed through peptide and receptor structural and sequence similarities, expression patterns, and physiolo...

show abstract

“…In this respect, intracellular signaling is thought to occur following endocytosis and nuclear translocation of peripherally ligated GPCRs; or following the activation of nuclear located GPCRs by endogenously produced non-secreted ligands (24). Nuclear localization has been documented in many GPCRs including the PTH receptor (25), a class B GPCR with 7TM sequence similarities to EMR2.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival

et al. 2011

View full text Add to dashboard Cite

Abstract. EGF-like module containing mucin-like hormone receptor 2 (EMR2) is a leukocyte-restricted adhesion G protein-coupled receptor. Aberrant expression of EMR2 and its highly homologous molecule CD97 have been reported in various human cancers. Herein, we investigate the expression of EMR2 in neoplastic breast human tissue and its relationship with patient survival. EMR2 expression in normal and neoplastic breast tissue was assessed by immunohistochemistry in sections from 10 normal controls and microarrayed tissue cores from 69 cases of ductal carcinoma in situ (DCIS) and 272 invasive carcinomas. The pattern and intensity of staining was correlated with the clinicopathological characteristics of each case and the disease outcome. While absent in normal breast epithelium, EMR2 was significantly up-regulated in the cytoplasmic and nuclear compartments of both DCIS and invasive carcinoma, with invasive samples displaying significantly higher expression levels compared with in situ disease. In invasive disease, EMR2 cytoplasmic expression was significantly associated with higher tumour grade but not with patient age, nodal status, tumour size, estrogen receptor expression, relapse-free or overall survival. In contrast, EMR2 nuclear expression correlated negatively with higher tumour grade. Of note, EMR2 nuclear expression was associated with longer relapse-free survival as well as overall survival. This study indicates that EMR2 is expressed in neoplastic breast epithelium and suggests that expression patterns of EMR2 are relevant in breast cancer progression. The association of improved patient survival with higher nuclear expression levels identifies EMR2 as a potential biomarker in patients with invasive breast cancer.

show abstract

Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation

Cited by 60 publications

References 28 publications

Role of Neurokinin 3 Receptors in Supraoptic Vasopressin and Oxytocin Neurons

Role of Neurokinin 3 Receptors in Supraoptic Vasopressin and Oxytocin Neurons

Agonist-independent Nuclear Localization of the Apelin, Angiotensin AT1, and Bradykinin B2 Receptors

Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival

Contact Info

Product

Resources

About