HGNC Approved Gene Symbol: NTSR2
Cytogenetic location: 2p25.1 Genomic coordinates (GRCh38) : 2:11,658,178-11,670,195 (from NCBI)
The tridecapeptide neurotensin (NTS; 162650) is widely distributed in various regions of the brain and in peripheral tissues. Its effects are mediated by specific membrane receptors, including neurotensin receptor-1 (NTSR1; 162651) and NTRS2 (Vita et al., 1998).
In a search for sequences homologous to NTSR1 in a rat hypothalamus cDNA library, Chalon et al. (1996) identified a novel neurotensin receptor, Ntsr2. Using the rat Ntsr2 cDNA as a probe to screen a human cortex cDNA library, Vita et al. (1998) identified human NTSR2 cDNA, which encodes a 410-amino acid protein that belongs to the G protein-coupled receptor family. NTSR2 shares 38% amino acid identity with human NTSR1 and over 75% amino acid identity with rat and mouse Ntsr2. NTSR2 contains a short cytoplasmic N-terminal sequence with no clear potential glycosylation sites. A cysteine residue is conserved in the human, mouse, and rat proteins in each of the extracellular loops between the 7 transmembrane domains. Threonine and serine residues that could be targets for phosphorylation are conserved in the human and rat proteins, as is a cysteine that could be a candidate for palmitoylation, thereby anchoring the region to the plasma membrane. Using Northern blot analysis, Vita et al. (1998) detected NTSR2 transcripts in adult brain regions including amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus, and thalamus. Using RT-PCR, they detected transcripts in cerebellum, kidney, uterus, heart, and lung.
Vita et al. (1998) demonstrated that ectopic expression of NTSR2 in CHO cells generated specific neurotensin-binding sites. The NTS affinity for NTSR2 receptor was slightly lower than the affinity for NTSR1. Levocabastine and 2 NTSR1 nonpeptide antagonists, SR142948A and SR48692, competed with NTS for NTSR2 receptor binding. Vita et al. (1998) found that NTS and levocabastine bind to recombinant NTSR2 expressed in CHO cells but do not elicit a second messenger response. However, SR48692 and SR142948A are potent agonists on the NTSR2 receptor and both compounds enhance inositol phosphate formation with subsequent intracellular calcium mobilization, induce arachidonic acid release, and stimulate mitogen-activated protein kinase (MAPK) activity. These activities were antagonized by NTS and levocabastine in a concentration-dependent manner. No effect was detected in cAMP formation following binding of SR142948A, SR48692, NTS, or levocabastine.
Using RT-PCR, immunofluorescence microscopy, and flow cytometric analysis, Saada et al. (2012) detected expression of NTS, NTSR1, NTSR2, and NTSR3 (SORT1; 602458) in primary human B lymphocytes and human B-cell lines at different stages of maturation. NTS exerted a proliferative and antiapoptotic effect on B cells. Patients with chronic B-cell lymphocytic leukemia (CLL; 151400) showed no expression of NTS and increased expression of NTSR2. Saada et al. (2012) concluded that NTS and its 2 specific receptors, NTSR1 and NTSR2, are expressed in human B lymphocytes, as previously found for T cells, macrophages, and dendritic cells, indicating that NTS may modulate immune responses and cell interactions.
Gross (2013) mapped the NTSR2 gene to chromosome 2p25.1 based on an alignment of the NTSR2 sequence (GenBank AY429107) with the genomic sequence (GRCh37).
Chalon, P., Vita, N., Kaghad, M., Guillemot, M., Bonnin, J., Delpech, B., Le Fur, G., Ferrara, P., Caput, D. Molecular cloning of a levocabastine-sensitive neurotensin binding site. FEBS Lett. 386: 91-94, 1996. [PubMed: 8647296] [Full Text: https://doi.org/10.1016/0014-5793(96)00397-3]
Gross, M. B. Personal Communication. Baltimore, Md. 6/13/2013.
Saada, S., Marget, P., Fauchais, A.-L., Lise, M.-C., Chemin, G., Sindou, P., Martel, C., Delpy, L., Vidal, E., Jaccard, A., Troutaud, D., Lalloue, F., Jauberteau, M.-O. Differential expression of neurotensin and specific receptors, NTSR1 and NTSR2, in normal and malignant human B lymphocytes. J. Immun. 189: 5293-5303, 2012. [PubMed: 23109725] [Full Text: https://doi.org/10.4049/jimmunol.1102937]
Vita, N., Oury-Donat, F., Chalon, P., Guillemot, M., Kaghad, M., Bachy, A., Thurneyssen, O., Garcia, S., Poinot-Chazel, C., Casellas, P., Keane, P., Le Fur, G., Maffrand, J. P. Soubrie, P.; Caput, D.; Ferrara, P.: Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells. Europ. J. Pharm. 360: 265-272, 1998. [PubMed: 9851594] [Full Text: https://doi.org/10.1016/s0014-2999(98)00678-5]