RGD Reference Report - Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells. - Rat Genome Database

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Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells.

Authors: Tfelt-Hansen, J  MacLeod, RJ  Chattopadhyay, N  Yano, S  Quinn, S  Ren, X  Terwilliger, EF  Schwarz, P  Brown, EM 
Citation: Tfelt-Hansen J, etal., Am J Physiol Endocrinol Metab 2003 Aug;285(2):E329-37. Epub 2003 Apr 15.
RGD ID: 1298591
Pubmed: PMID:12700162   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00489.2002   (Journal Full-text)

Elevated extracellular calcium ([Ca2+]o) and other agonists potentially acting via the calcium-sensing receptor (CaR) increase parathyroid hormone-related peptide (PTHrP) release from H-500 Leydig cells. Here, we provide strong evidence for the CaR's involvement by using a dominant negative CaR that attenuates high [Ca2+]o-induced PTHrP release. This effect is likely transcriptional, because high [Ca2+]o upregulates the PTHrP transcript, an effect that is abolished by actinomycin D. Regulation of PTHrP release by the CaR involves activation of PKC as well as ERK1/2, p38 MAPK, and JNK pathways. However, we show for the first time that high [Ca2+]o-induced activation of the stress-activated protein kinase SEK1 is PKC independent, because there is an additive effect of a PKC inhibitor in combination with the JNK inhibitor on [Ca2+]o-stimulated PTHrP release. Furthermore, high [Ca2+]o, in a PKC-independent fashion, induces phosphorylation of ERK1/2, SEK1, p38 MAPK, and its downstream transcription factor ATF-2. We conclude that CaR regulation of PTHrP release in H-500 cells involves activation of PKC as well as the ERK1/2, p38 MAPK, and JNK pathways.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell population proliferation  IMP 1298591 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casr  (calcium-sensing receptor)

Objects referenced in this article
Gene Mapk1 mitogen activated protein kinase 1 Rattus norvegicus
Gene Mapk14 mitogen activated protein kinase 14 Rattus norvegicus
Gene Mapk3 mitogen activated protein kinase 3 Rattus norvegicus
Gene Pthlh parathyroid hormone-like hormone Rattus norvegicus
Gene Tnf tumor necrosis factor Rattus norvegicus

Additional Information