Interaction of the parathyroid hormone receptor with the 14-3-3 protein

• Published in: Biochimica et biophysica acta Vol. 1620; no. 1; pp. 32 - 38
• Main Authors: Tazawa, Hiroshi, Takahashi, Shu, Zilliacus, Johanna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.03.2003
• Subjects: 14-3-3; 14-3-3 Proteins; Amino Acid Sequence; Animals; COS Cells; Cyclic AMP-Dependent Protein Kinases - pharmacology; Escherichia coli - metabolism; Green Fluorescent Proteins; Luminescent Proteins; Microscopy, Confocal; Molecular Sequence Data; Nuclear localization; Parathyroid hormone; Phosphorylation; Plasmids; Protein Binding; Protein interaction; Receptors, Parathyroid Hormone - chemistry; Receptors, Parathyroid Hormone - genetics; Receptors, Parathyroid Hormone - metabolism; Signal Transduction; Transfection; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; 14-3-3; Phosphorylation; Nuclear localization; Protein interaction; Parathyroid hormone
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(02)00503-2

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.