Cyclic 3,5 adenoise monophosphate and cyclosporin A inhibit cellular proliferation and serine/threonine protein phosphatase activity in pituitary cells

Tullio Florio, Brian A. Perrino, Philip J.S. Stork

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

cAMP and cyclosporin A exert antiproliferative effects in many different cell types. In cultured pituitary cells, the antiproliferative effects of both agents correlate with the inhibition of a serine/threonine protein phosphatase activity. This inhibition is mediated by the heat-stable protein, inhibitor-1. The increase of cAMP levels, through the activation of the protein kinase A, induces inhibitor-1 phosphorylation and activation. On the other hand, cyclosporin A, inhibiting the calcium-dependent serine/threonine phosphatase calcineurin, prevents the dephosphorylation and inactivation of inhibitor-1. This dual regulation by cAMP and calcium on the inhibitor 1 activity parallel the effects of these agents on DNA synthesis and serine/threonine phosphatase activity. Because inhibitor-1 is the main regulator of protein phosphatase 1 activity, these results suggest that protein phosphatase 1 may be the common target of cAMP and cyclosporin A in regulating cell proliferation. We propose that protein-phosphatase 1 stimulates growth in these cells and that cAMP and cyclosporin A block this effect through their actions on inhibitor-1.

Original languageEnglish (US)
Pages (from-to)4409-4418
Number of pages10
JournalEndocrinology
Volume137
Issue number10
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology

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