Parathyroid hormone 1-34, but not 3-34 or 7-34, transiently translocates protein kinase C in cultured renal (OK) cells.
While protein kinase C (PKC) appears to play a role in the action of PTH in renal cells, direct evidence of activation by PTH is lacking. Rat PTH (1-34) caused a rapid, transient translocation of PKC in opossum kidney (OK) cells from a basal value of 0.09 to maximum of 0.24 at 10-15 sec. Both the time course and dose-response relationship of translocation matched a corresponding increase in cytosolic Ca2+. In contrast, PTH activation of cAMP-dependent protein kinase (PKA), while also rapid, was greater in magnitude (0.10 to 0.50), persistent, and occurred at a threshold level of 3 x 10(-10)M PTH, compared to 10(-8)M for PKC. Neither bPTH(3-34) nor bPTH(7-34) activated either protein kinase, while both antagonized rPTH(1-34)-induced PKC translocation more effectively than PKA activation. These differential effects of PTH agonist and antagonists further support the suggestion that PTH acts through two signal transduction mechanisms in which one or more receptors is linked in distinct ways to adenylate cyclase and phospholipase C.
Tamura
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Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MD 21224.
Sakamoto
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D000818:Animals; D002460:Cell Line; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013329:Structure-Activity Relationship; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C058350:parathyroid hormone (7-34); D019379:Teriparatide; C031617:parathyroid hormone (3-34); D011494:Protein Kinases; D011493:Protein Kinase C