Protein kinase C‐activating domains of parathyroid hormone‐related protein

• Published in: Journal of bone and mineral research Vol. 8; no. 4; pp. 497 - 503
• Main Authors: Gagnon, Lyne, Jouishomme, Hervé, Whitfield, James F., Durkin, Jon P., MacLean, Susanne, Neugebauer, Witold, Willick, Gordon, Rixon, Ray H., Chakravarthy, Balu
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01-04-1993; American Society for Bone and Mineral Research
• Subjects: Adenylyl Cyclases - metabolism; Amino Acid Sequence; Animals; Binding Sites; Biological and medical sciences; Bone and Bones - enzymology; Enzyme Activation - physiology; Fundamental and applied biological sciences. Psychology; Humans; Molecular Sequence Data; Osteosarcoma; Parathyroid Hormone - physiology; Parathyroid Hormone-Related Protein; Peptide Fragments; Phosphorylation; Protein Kinase C - metabolism; Proteins - physiology; Rats; Skeleton and joints; Tumor Cells, Cultured; Vertebrates: osteoarticular system, musculoskeletal system; Cell culture; Protein kinase C; Rat; Enzyme; Rodentia; N terminal peptide; Osteoarticular system; Parathormone; Vertebrata; Mammalia; Enzymatic activity; Parathyroid hormone; Established cell line; Hormonal regulation; Skeleton
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.5650080414

N‐terminal fragments of PTH‐related protein (PTHrP), PTHrP‐(1–34), and PTHrP‐(1–40) stimulated both adenylyl cyclase and a mechanism that increases membrane‐associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. There were two peaks in the PKC response to the N‐terminal PTHrP fragments: one peak was obtained with picomolar and the other with nanomolar PTHrP concentrations. The PKC‐stimulating picomolar concentrations of the PTHrP fragments did not detectably stimulate adenylyl cyclase, but the nanomolar concentrations did. Since a similar two‐peak response of PKC activity was obtained with PTHrP‐(28–34), the single, N‐terminal PKC activation domain of the PTHrP is in the same 28–34 region of the molecule as that of PTH despite this region having different primary amino acid sequences in the two hormones. Unlike PTH, PTHrP has a second PKC activation domain, as indicated by the ability of picomolar concentrations of the PTHrP‐(107–111) fragment to stimulate maximally membrane‐associated PKC activity in the osteosarcoma cells.