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Protein kinase C‐activating domains of parathyroid hormone‐related protein
Author(s) -
Gag Lyne,
Jouishomme Hervé,
Whitfield James F.,
Durkin Jon P.,
MacLean Susanne,
Neugebauer Witold,
Willick Gordon,
Rixon Ray H.,
Chakravarthy Balu
Publication year - 1993
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.5650080414
Subject(s) - adenylyl cyclase , protein kinase c , parathyroid hormone related protein , parathyroid hormone , chemistry , medicine , endocrinology , protein kinase a , signal transduction , kinase , microbiology and biotechnology , biology , biochemistry , calcium
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.