Differential regulation of the PTH/PTHrP receptor and its mRNA in human osteoblast-like SaOS-2 cells

Autor: F. Richard Bringhurst, Shoichi Fukayama, Armen H. TashijianJr
Rok vydání: 1994
Předmět:
Zdroj: Journal of Bone and Mineral Metabolism. 12:S175-S181
ISSN: 1435-5604
0914-8779
DOI: 10.1007/bf02375699
Popis: Using wild-type SaOS-2 cells and a mutant cAMP-resistant subclone Ca#4A, we have recently shown that homologous down-regulation of PTH/PTHrP receptor (PTH/PTHrPR) is mediated by mechanisms independent of PKA activation, and that homologous down-regulation of PTH/PTHrPR mRNA occurs later than the decline in functional cell surface receptors via a mechanism that does not involve enhanced mRNA degradation or new protein synthesis but does depend on cAMP/PKA. Treatment of SaOS-2 cells with [Arg2]hPTH(1-34) or hPTH(3-34) for 24 h, both of which bind to the human PTH/PTHrPR as well as hPTH(1-34) but fail to stimulate cAMP/PKA efficiently, does not cause down-regulation of PTH/PTHrPR mRNA; however, the same treatment did down-regulate PTH/PTHrPR protein. Incubation with isoproterenol for 24 h, which activates both PKA andβ-adrenergic receptor kinase (βARK) in these cells, induced significant down-regulation of both the PTH/PTHrPR and its mRNA. However, treatment with vasoactive intestinal peptide (VIP) or PGE2 for 24 h, both of which stimulate the cAMP/PKA pathway in these cells, did not down-regulate PTH/PTHrPR mRNA. We conclude that both PKA-dependent and -independent (such asβARK) mechanisms are required for regulation of the PTH/PTHrPR and its mRNA.
Databáze: OpenAIRE
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