Protein kinase C-activating domains of parathyroid hormone-related protein.
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.
Gagnon
L
L
Cell Systems Section, National Research Council of Canada, Ottawa, Ontario.
Jouishomme
H
H
Whitfield
J F
JF
Durkin
J P
JP
MacLean
S
S
Neugebauer
W
W
Willick
G
G
Rixon
R H
RH
Chakravarthy
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); D011493:Protein Kinase C; D000262:Adenylyl Cyclases