RGD Reference Report - Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. - Rat Genome Database

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Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.

Authors: Koh, J  Dar, M  Untch, BR  Dixit, D  Shi, Y  Yang, Z  Adam, MA  Dressman, H  Wang, X  Gesty-Palmer, D  Marks, JR  Spurney, R  Druey, KM  Olson JA, JR 
Citation: Koh J, etal., Mol Endocrinol. 2011 May;25(5):867-76. doi: 10.1210/me.2010-0277. Epub 2011 Mar 10.
RGD ID: 7207228
Pubmed: PMID:21393447   (View Abstract at PubMed)
PMCID: PMC3082322   (View Article at PubMed Central)
DOI: DOI:10.1210/me.2010-0277   (Journal Full-text)

The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased expression of the calcium-sensing receptor (CaSR), a G protein-coupled receptor. However, CaSR expression is highly variable in parathyroid adenomas, and the lack of correlation between CaSR abundance and calcium-responsive PTH kinetics indicates that mechanisms independent of CaSR expression may contribute to aberrant calcium sensing in parathyroid disease. To gain a better understanding of parathyroid tumors and the molecular determinants that drive parathyroid adenoma development, we performed gene expression profiling on a panel of 64 normal and neoplastic parathyroid tissues. The microarray data revealed high-level expression of genes known to be involved in parathyroid biology (PTH, VDR, CGA, CaSR, and GCM2). Moreover, our screen identified regulator of G protein signaling 5 (RGS5) as a candidate inhibitor of CaSR signaling. We confirmed RGS5 to be highly expressed in parathyroid adenomas relative to matched-pair normal glands. Transient expression of RGS5 in cells stably expressing CaSR resulted in dose-dependent abrogation of calcium-stimulated inositol trisphosphate production and ERK1/2 phosphorylation. Furthermore, we found that RGS5-nullizygous mice display reduced plasma PTH levels, an outcome consistent with attenuated opposition to CaSR activity. Collectively, these data suggest that RGS5 can act as a physiological regulator of calcium sensing by CaSR in the parathyroid gland. The abnormally elevated expression of RGS5 observed in parathyroid adenomas could thus represent a novel mechanism of CaSR desensitization in patients with primary hyperparathyroidism.

Objects Annotated

Genes (Rattus norvegicus)
Rgs5  (regulator of G-protein signaling 5)

Genes (Mus musculus)
Rgs5  (regulator of G-protein signaling 5)

Genes (Homo sapiens)
RGS5  (regulator of G protein signaling 5)


Additional Information