Interaction of the parathyroid hormone receptor with the 14-3-3 protein.
The receptor for parathyroid hormone (PTH) and PTH-related protein (PTHrP) regulates calcium homeostasis, bone remodeling and skeletal development. 14-3-3 proteins bind to signaling proteins and act as molecular scaffolds and regulators of subcellular localization. We show that the parathyroid hormone receptor (PTHR) interacts with 14-3-3 and the proteins colocalize within the cell. 14-3-3 interacts with the C-terminal tail of the receptor containing a consensus 14-3-3 binding motif, but additional binding sites are also used. Protein kinase-A treatment of the receptor and especially the C-terminal tail reduces 14-3-3 binding. The expressed C-terminal tail is primarily localized in the nucleus, supporting the function of a putative nuclear localization signal that could be involved in the previously described nuclear localization of PTHR. The observed interaction between PTHR and the 14-3-3 protein implies that 14-3-3 could contribute to regulation of PTHR signaling.
Tazawa
Hiroshi
H
Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden.
Takahashi
Shu
S
Zilliacus
Johanna
J
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids; D011485:Protein Binding; D018016:Receptors, Parathyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D048948:14-3-3 Proteins; D008164:Luminescent Proteins; D018016:Receptors, Parathyroid Hormone; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases