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β‐Adrenergic receptor kinase‐like activity and β‐arrestin are expressed in osteoblastic cells
Author(s) -
Bliziotes Michael,
Murtagh James,
Wiren Kristine
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110613
Subject(s) - homologous desensitization , arrestin , parathyroid hormone , biology , receptor , desensitization (medicine) , adenylyl cyclase , gs alpha subunit , microbiology and biotechnology , protein kinase a , g protein coupled receptor , rhodopsin , beta adrenergic receptor kinase , g protein , phosphorylation , endocrinology , medicine , biochemistry , calcium , retinal
Biologic responses to peptide calciotropic hormones, such as parathyroid hormone (PTH) and calcitonin, exhibit desensitization. As with most hormones, however, the mechanisms of desensitization are not completely understood. For the β 2 ‐adrenergic receptor (β 2 AR) system, which is coupled to adenylyl cyclase via the stimulatory guanine nucleotide‐binding regulatory (G s ) protein, homologous desensitization is mediated in part by a receptor‐specific kinase (βARK) and a soluble cofactor (β‐arrestin). Recently, this system has been reported to be involved in rapid homologous desensitization of the PTH/parathyroid hormone receptor protein (PTHrP) receptor. We have identified the presence of this system in bone using reverse‐transcriptase PCR. Nucleotide sequence of PCR fragments from ROS 17/2.8 cells revealed 100% identity with rat brain βARK1 and β‐arrestin 1 sequences. Northern analyses with RNA from ROS 17/2.8, UMR 106‐H5 cells, and primary cultures of nontransformed neonatal rat calvariae demonstrated two mRNA species of 4 and 2.6 kilobases (kb) for βARK and 7.5 kb for β‐arrestin, comparable to those found in bovine brain. βARK‐like activity was demonstrated in cytosolic extracts of the UMR 106‐H5 cells by assessing phosphorylation of the retinal photoreceptor, rhodopsin, by the extracts. Phosphorylation was enhanced with light‐activated rhodopsin and by bovine brain G βγ subunits; heparin inhibited phosphorylation. These findings are characteristic of βARK. Expression of β‐arrestin in the UMR 106‐H5 cells was confirmed by immunoblot. Thus, osteoblastic cells express proteins, βARK, and β‐arrestin, which may regulate desensitization of calciotropic hormone receptors.