Changing serine-485 to alanine in the opossum parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of phospholipase C in a stably transfected human kidney cell line: a useful model for PTH-analog screening?
Bone
; 28(2): 182-6, 2001 Feb.
Article
in En
| MEDLINE
| ID: mdl-11182376
ABSTRACT
Using site-directed mutagenesis, we have introduced a serine-485-to-alanine mutation in the opossum parathyroid hormone (PTH) receptor. This amino acid is considered to be phosphorylated by protein kinase A upon ligand binding. Both wild-type (WT) and mutant receptor were stably expressed in 293-EBNA HEK cells. The mutant receptor showed comparable binding characteristics and only a slight increase in cAMP production compared with WT. However, the PTH dose-dependent increase in inositol phosphate production was 24-fold for the mutant receptor vs. 6-fold for the WT receptor. This mutant might prove useful in the sensitive detection of phospholipase C activation through various ligands, as the PTH receptor becomes a target of therapeutic intervention in osteoporosis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parathyroid Hormone
/
Peptide Fragments
/
Type C Phospholipases
/
Receptors, Parathyroid Hormone
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Bone
Journal subject:
METABOLISMO
/
ORTOPEDIA
Year:
2001
Document type:
Article
Affiliation country:
Germany