Parathyroid hormone inhibits c-Jun N-terminal kinase activity in rat osteoblastic cells by a protein kinase A-dependent pathway.
Treatment of osteoblastic cells with PTH initiates dual signaling cascades resulting in activation of both PKA and PKC. It has been shown that PTH either inhibits or stimulates ERKs depending on dose of the hormone; nevertheless, the ability of PTH to regulate other members of the MAPK family is unknown. Another member of this family, c-Jun-NH(2)-terminal kinase (JNK), is preferentially activated by cytokines and cellular stresses and plays a key role in regulating the activity of various transcription factors. We demonstrate that treatment of UMR 106-01 cells and rat calvarial osteoblasts with PTH (10(-8) M), N-terminal peptides of PTH that selectively activate PKA, or 8-bromo-cAMP (activates PKA) results in the inhibition of JNK activity from high basal levels. Examination of the upstream members of the JNK cascade revealed that both stress-activated protein kinase/extracellular signal-related kinase kinase 1/MAPK kinase 4 and MAPK/extracellular signal-related kinase kinase kinase 1 activities were also inhibited after treatment with PTH (10(-8) M). We conclude that treatment of osteoblastic cells with PTH is sufficient to inhibit high basal JNK activity by activation of the PKA signaling cascade.
Doggett
Teresa A
TA
Cell and Molecular Biology Program, Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Swarthout
John T
JT
Jefcoat
Stephen C
SC
Wilhelm
Dagmar
D
Dieckmann
Andreas
A
Angel
Peter
P
Partridge
Nicola C
NC
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019379:Teriparatide / Q000494:pharmacology*; D054462:p21-Activated Kinases
D019379:Teriparatide; C515906:Pak1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases