In a continuous line of rat thyroid cells transformed by the k-ras oncogene (KiKi), the expression of rasp21 correlates with an increased activity of a phosphoinositide- specific phospholipase AB, which leads to elevated levels of glycerophosphoinositols. In this study we have characterized bthioel ogical activities of these compounds. Growth and differentiation in thyroid cells are mainly regulated by the activation of adenylylcyclase. Therefore,w e haves tudied the effects of glycerophosphoinositols on the activity of this enzyme using a normal thyroid cell line (FRTL5M).i cromolar concentrations of glycerophosphoinositol 4- phosphate (GroPIns-4-P) caused a -50% inhibition of the adenylylcyclase activity in FRTL5 membranes stimulated by the GTP-binding protein activaftlouro - roaluminate. Similar concentrations of GroPIns-4-P were detected in KiKi cells but not in the normal FRTLS line. Micromolar GroPIns-4-P was found to be taken up by intact FRTL5 cells and to induce nearly 50% inhibition of the thyrotropin- and cholera toxin-induced increase in cAMP levels. Similar results were also observed in other cell lines (smooth muscle, pituitary cells, and pneumocytes). GroPIns-4-P inhibitedC AMPdependent cellular functions sucahs iodide uptake and thymidine incorporation in FRTL5 cells when stimulated by thyrotropin and cholera toxin but not when induced by forskolin. Theser esults arec onsistent with GroPIns-4-P exerting an inhibitoerfyf ect on the GTPbinding protein that stimulateasd enylylcyclase. We propose that GroPIns-4-Pm ight mediatea mechanism of cross-talk between adenylylcyclase anphdo spholipase A2 in thyroida s well as in otherc ell systems.

Glycerophosphoinositol 4-phosphate, a putative endogenous inhibitor of adenylyl cyclase / Iacovelli, Luisa; Falasca, M; Valitutti, S; D'Arcangelo, D; Corda, D.. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 268:(1993), pp. 20402-20407.

Glycerophosphoinositol 4-phosphate, a putative endogenous inhibitor of adenylyl cyclase.

IACOVELLI, LUISA;
1993

Abstract

In a continuous line of rat thyroid cells transformed by the k-ras oncogene (KiKi), the expression of rasp21 correlates with an increased activity of a phosphoinositide- specific phospholipase AB, which leads to elevated levels of glycerophosphoinositols. In this study we have characterized bthioel ogical activities of these compounds. Growth and differentiation in thyroid cells are mainly regulated by the activation of adenylylcyclase. Therefore,w e haves tudied the effects of glycerophosphoinositols on the activity of this enzyme using a normal thyroid cell line (FRTL5M).i cromolar concentrations of glycerophosphoinositol 4- phosphate (GroPIns-4-P) caused a -50% inhibition of the adenylylcyclase activity in FRTL5 membranes stimulated by the GTP-binding protein activaftlouro - roaluminate. Similar concentrations of GroPIns-4-P were detected in KiKi cells but not in the normal FRTLS line. Micromolar GroPIns-4-P was found to be taken up by intact FRTL5 cells and to induce nearly 50% inhibition of the thyrotropin- and cholera toxin-induced increase in cAMP levels. Similar results were also observed in other cell lines (smooth muscle, pituitary cells, and pneumocytes). GroPIns-4-P inhibitedC AMPdependent cellular functions sucahs iodide uptake and thymidine incorporation in FRTL5 cells when stimulated by thyrotropin and cholera toxin but not when induced by forskolin. Theser esults arec onsistent with GroPIns-4-P exerting an inhibitoerfyf ect on the GTPbinding protein that stimulateasd enylylcyclase. We propose that GroPIns-4-Pm ight mediatea mechanism of cross-talk between adenylylcyclase anphdo spholipase A2 in thyroida s well as in otherc ell systems.
1993
01 Pubblicazione su rivista::01a Articolo in rivista
Glycerophosphoinositol 4-phosphate, a putative endogenous inhibitor of adenylyl cyclase / Iacovelli, Luisa; Falasca, M; Valitutti, S; D'Arcangelo, D; Corda, D.. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 268:(1993), pp. 20402-20407.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/141112
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