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Titolo:
INHIBITION OF SERINE THREONINE PROTEIN PHOSPHATASES ENHANCES AGONIST-STIMULATED CAMP ACCUMULATION IN UMR-106 OSTEOBLAST-LIKE CELLS
Autore:
KOVACS CS; CHIK CL; LI B; KARPINSKI E; HO AK;
Indirizzi:
UNIV ALBERTA,DEPT PHYSIOL,726 MED SCI BLDG EDMONTON AB T6G 2H7 CANADA UNIV ALBERTA,DEPT PHYSIOL EDMONTON AB T6G 2H7 CANADA UNIV ALBERTA,DEPT MED,DIV ENDOCRINOL EDMONTON AB T6G 2H7 CANADA
Titolo Testata:
Molecular and cellular endocrinology
fascicolo: 1-2, volume: 110, anno: 1995,
pagine: 9 - 16
SICI:
0303-7207(1995)110:1-2<9:IOSTPP>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
OKADAIC ACID; PARATHYROID-HORMONE; ADENYLATE-CYCLASE; CALYCULIN-A; KINASE-C; BONE-RESORPTION; DEPHOSPHORYLATION; TAUTOMYCIN; RECEPTOR; PEPTIDE;
Keywords:
CALYCULIN A; CAMP; OKADAIC ACID; OSTEOBLASTS; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN KINASE C; TAUTOMYCIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
C.S. Kovacs et al., "INHIBITION OF SERINE THREONINE PROTEIN PHOSPHATASES ENHANCES AGONIST-STIMULATED CAMP ACCUMULATION IN UMR-106 OSTEOBLAST-LIKE CELLS", Molecular and cellular endocrinology, 110(1-2), 1995, pp. 9-16

Abstract

Protein phosphatases regulate the activity of signal transduction mechanisms by dephosphorylating activated components. By utilizing selective inhibitors of these phosphatases, we investigated their role in regulating cAMP accumulation in the UMR 106 osteoblast-like tumor cell line. PTHrP, PTH and PGE(2) stimulated cAMP accumulation up to 100-fold. Calyculin A, a potent inhibitor of protein phosphatase type 1 (PPI) and type 2A (PP2A), did not affect basal levels of cAMP, but concentrations of 10(-11) M to 10(-8) M increased PTHrP-, PTH- and PGE(2)-stimulated cAMP accumulation up to 1.7-fold, and this increase was concentration-dependent. Similar results were obtained with tautomycin, another potent inhibitor of PP1 and PP2A. In contrast, okadaic acid, a potent inhibitor of PP2A which inhibited PP1 less potently, did not enhancePTHrP-, PTH-, or PGE(2)-stimulated cAMP accumulation. The effect of calyculin A on agonist-stimulated cAMP accumulation persisted in cells treated with isobutyl methylxanthine, a phosphodiesterase inhibitor. When the effect of calyculin A was compared with that of 4 beta-phorbol12-myristate 13-acetate (PMA), it was found that while PMA enhanced both the receptor and forskolin-stimulated cAMP accumulation, calyculinA had no effect on the forskolin-stimulated cAMP accumulation. The effect of calyculin A on PTHrP- and PTH-stimulated cAMP accumulation persisted in cells treated with PMA. These results suggest that protein phosphatases play an important role in agonist-stimulated cAMP accumulation in osteoblastlike cells, and that PPI but not PP2A may tie the major phosphatase involved. In contrast to activation by protein kinase C, the site of action for the phosphatase appears to be predominantly at a step prior to the activation of adenylyl cyclase in the cAMP signal transduction pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 14:22:40