Role of protein kinase A, phospholipase C and phospholipase D in parathyroid hormone receptor regulation of protein kinase Calpha and interleukin-6 in UMR-106 osteoblastic cells.
Parathyroid hormone (PTH) stimulates both bone formation and resorption by activating diverse osteoblast signalling pathways. Upstream signalling for PTH stimulation of protein kinase C-alpha (PKCalpha) membrane translocation and subsequent expression of the pro-resorptive cytokine interleukin-6 (IL-6) was investigated in UMR-106 osteoblastic cells. PTH 1-34, PTH 3-34, PTHrP and PTH 1-31 stimulated PKCalpha translocation and IL-6 promoter activity. Pharmacologic intervention at the adenylyl cyclase (AC) pathway (forskolin, IBMX, PKI) failed to alter PTH 1-34- or PTH 3-34-stimulated PKCalpha translocation. The phosphoinositol-phospholipase C (PI-PLC) antagonist U73122 slightly decreased PTH 1-34-stimulated PKCalpha translocation; however, the control analogue U73343 acted similarly. Propranolol, an inhibitor of phosphatidic acid (PA) phosphohydrolase, decreased diacylglycerol (DAG) formation and attenuated PTH 1-34- and PTH 3-34-stimulated PKCalpha translocation and IL-6 promoter activity, suggesting a phospholipase D (PLD)-dependent mechanism. This is the first demonstration that PLD-mediated signalling leads to both PKC-alpha translocation and IL-6 promoter activation in osteoblastic cells.
Radeff
Julie M
JM
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611, USA.
Singh
Amareshwar T K
AT
Stern
Paula H
PH
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000201:enzymology; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004075:Diglycerides / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000201:enzymology*; D010012:Osteogenesis / Q000502:physiology; D010281:Parathyroid Hormone / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D051381:Rats; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D044168:Receptor, Parathyroid Hormone, Type 1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D010711:Phosphatidate Phosphatase; D010738:Type C Phospholipases; D010739:Phospholipase D