Disease relevance of CALCR

• The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome [1].
• Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line [2].
• A human ovarian small cell carcinoma line (BIN-67) expresses abundant calcitonin (CT) receptors (CTR) (143,000 per cell) that are coupled, to adenylate cyclase [2].
• MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATc1, and calcitonin receptor-positive but require receptor activator of NFkappaB ligand for bone resorption [3].
• In conclusion, the CTR allele is one of the genetic factors regulating body weight in Japanese women [4].

Psychiatry related information on CALCR

• These results suggest that N-PCT can function as an endogenous ligand for the CT receptor and may act as a catabolic signaling molecule in the central regulation of feeding behavior and energy homeostasis [5].
• The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody-seronegative controls on simple (SRT) and choice (CRT) reaction time tasks [6].
• For the patients with Huntington's disease, this CRT/SRT difference was not significant [7].
• There was no instance of ventricular proarrhythmia associated with atrial shock therapies, undersensing of ventricular arrhythmias, or interruption of CRT therapy associated with the combined device [8].
• In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory) [9].

High impact information on CALCR

• Mutants in CTR1 exhibit a constitutive ethylene-response phenotype [10].
• Both the ethylene receptors and CTR1 are negative regulators of ethylene responses [10].
• Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP [11].
• Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family [12].
• Thr-4 residues of the CTR repeats are functionally important phosphorylation sites [13].

Chemical compound and disease context of CALCR

• All children were free of CNS disease at diagnosis and had been randomly assigned to receive CNS prophylaxis with either 1,800 cGy cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or IT MTX plus intravenous (IV) high-dose MTX (HDMTX) [14].
• Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells [15].
• We conclude that in breast cancer cells, the calcitonin receptor and the adenylate cyclase are coupled by at least one Go/Gi-protein sensitive to growth-regulating agents; this results in a modulation of the cyclic AMP response to calcitonin by these agents [16].
• CONCLUSIONS: Results show that the polymorphism in the calcitonin receptor gene could be a genetic marker for urinary stone disease and therefore it is worthwhile pursuing further studies of the leucine allele of calcitonin receptor gene due to it is strongly correlated with stone disease [17].
• Six hundred thirty-four children with acute lymphoblastic leukemia (ALL) were randomized to receive sanctuary therapy consisting of either cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or three courses of intermediate-dose methotrexate (IDM) plus intrathecal methotrexate [18].

Biological context of CALCR

• Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction [19].
• The amino acid sequence of the hCTR is 73% identical to the pCTR, although the hCTR contains an insert of 16 amino acids between transmembrane domain I and II [2].
• We localized the human CTR gene to chromosome 7 in band q22 [19].
• To clone a human CTR (hCTR), a BIN-67 cDNA library was screened using a cDNA probe from a porcine renal CTR (pCTR) that we recently cloned [2].
• Here, we studied the features of homologous down-regulation of the CTR in mature mouse OCLs [20].

Anatomical context of CALCR

• Expression of all three CTR isoforms in COS cells demonstrated that GC-2 has a lower binding affinity for salmon (s) CT (Kd approximately 15 nM) than GC-10 or o-hCTR (Kd approximately 1.5 nM) [19].
• Physiological levels of calcitonin regulate the mouse osteoclast calcitonin receptor by a protein kinase Alpha-mediated mechanism [20].
• A novel calcitonin receptor gene in human osteoclasts from normal bone marrow [21].
• The RT-PCR results indicated that the 5'-untranslated region (5'UTR) was different between CTR mRNAs in human osteoclasts and in a mammary tumor cell line, MCF-7 cells [21].
• We have mapped the CTR gene (CALCR) to chromosome band 7q21.3 by polymerase chain reaction and single-strand conformation analysis of somatic cell hybrids as well as fluorescence in situ hybridization (FISH) to metaphase chromosome spreads [1].

Associations of CALCR with chemical compounds

• The expressed hCTR was coupled to adenylate cyclase [2].
• Attenuation of CT-induced CTR down-regulation by the competitive cAMP antagonist, RpcAMP, and high concentrations of H-7, but not by protein kinase C-specific inhibitors (sphingosine, staurosporine, and a lower concentration of H-7), suggested that the PKA pathway is primarily involved in homologous regulation of the CTR [20].
• Biological activity of immunoreactive human and mouse IAPP components derived from pancreatic extracts was assessed by calcitonin receptor-mediated stimulation of cyclic AMP accumulation in T47D human breast carcinoma cells [22].
• Calcitonin receptor mRNA expression in TT cells: effect of dexamethasone [23].
• Two alleles of the calcitonin receptor gene ( CTR ) exist: a base mutation T-->C in the third intracellular C-terminal domain changes a proline (CCG) at position 447 to a leucine (CTG) [24].
• Deletion and/or alanine replacement of the region of the calcitonin receptor between residues 150 and 153 resulted in marked reduction in cAMP responses to these compounds, with some compound-specific differences observed, supporting a critical role for this region [25].

Physical interactions of CALCR

• CHO-P cells provide an environment conducive to a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is imperative for amylin binding [26].
• The distinct functional characteristics of GC-2 and GC-10, which differ in structure only in the first intracellular domain, indicate that the first intracellular domain of the CTR plays a previously unidentified role in modulating ligand binding and signal transduction via the G protein/adenylate cyclase system [19].
• In a two-hybrid screening, we found that the actin-binding protein filamin interacted with the C-terminal tail of the CTR [27].
• These studies suggest that CGRP initially interacts with the calcitonin receptor to produce a calcitonin-like effect, which is followed by hypercalcaemia presumably by antagonising the action of endogenous circulating calcitonin [28].
• Thus, membrane-bound TcCRT interacts with the collagenous portion Clq, and this Clq is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization [29].

Regulatory relationships of CALCR

• Cotransfection with calcitonin receptor (CTR)I1- induced cell surface expression of RAMP 1 [30].
• Islet amyloid polypeptide stimulates cyclic AMP accumulation via the porcine calcitonin receptor [31].
• Immunocytochemical staining of mirror image sections showed that some CT-secreting cells also expressed CT receptor [32].
• The cells expressing CT-R mRNA in primary tumors also co-expressed PCNA [33].
• Phospholipase D- and protein kinase C isoenzyme-dependent signal transduction pathways activated by the calcitonin receptor [34].

Other interactions of CALCR

• Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product [30].
• Thus, this study reveals important functionality of the RAMP C-terminal domain and identifies key differences in the role of the RAMP C terminus for CTR versus CLR-based receptors [35].
• Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins [36].
• The CTa (shorter form) calcitonin receptor, dimerized with RAMP1 [amylin 1 (a) receptor], appears to represent binding sites at the nucleus accumbens and the subfornical organ [37].
• In combined analysis of the VDR genotype (B,b) and the CTR genotype (C,T), the body height was found to be significantly different between CCB and others (P = 0.0236) [4].

Analytical, diagnostic and therapeutic context of CALCR

• In situ hybridization on GCT tissue sections demonstrated CTR mRNA expression in osteoclast-like cells [19].
• Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene [38].
• In this study, the genotypes of the CTR and their relationship with the body height, the body weight, the bone mineral density (BMD), and osteocalcin levels were examined in 152 healthy Japanese women aged 16-43 years [4].
• To determine the CALCR genotype PCR amplification followed by digestion with Alul restriction enzyme were carried out according to Nakamura et al [39].
• In a cross-sectional study we investigated the potential association between CALCR polymorphism (C1377T) and bone mineral density in 114 postmenopausal women [40].

References