Beta-adrenergic receptor kinase-1 acutely regulates PTH/PTHrP receptor signalling in human osteoblastlike cells.

Abstract:

:To investigate whether G protein-coupled receptor kinases (GRKs) are involved in the regulation of the PTH/PTHrPR, we have established mutant SaOS-2 cells which stably overexpress (> 10-20-fold) a dominant negative form of the beta-adrenergic receptor kinase-1 (beta ARK-1). Acute (< or = 2 h) incubation with hPTH (1-34) induced significantly less (by up to 50%) downregulation of the PTH/PTHrPR in beta ARK-1 mutant SaOS-2 cells than observed in wild-type cells. Pretreatment of wild-type cells with PTH for 2 h induced homologous cAMP desensitisation to a second challenge with PTH, while the effect was blunted by up to 60% in beta ARK-1 mutant cells. We conclude that activation of beta ARK-1 (or a closely related GRK) is a critical component of the acute phase (< or = 2 h) of PTH-induced receptor downregulation and homologous cAMP desensitisation of the PTH/PTHrPR.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Fukayama S,Kong G,Benovic JL,Meurer E,Tashjian AH Jr

doi

10.1016/s0898-6568(97)00044-2

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

469-74

issue

6

eissn

0898-6568

issn

1873-3913

pii

S0898656897000442

journal_volume

9

pub_type

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