Parathyroid hormone induction of c-fos expression requires phosphorylation of creb at serine 133 by protein kinase A

Darren R. Tyson, Nicola C. Partridge

Research output: Contribution to journalArticle

Abstract

c-fos is induced in response to parathyroid horinonr (PTH) in a (AMP-depetident manner in the rat osteosarroina cell line UMR 106-01. PTH treatment leads to the phosphorylation of the cAMP response element binding prutrinf(CREB) at M-rine 133 (pCRKB) which binds the major CHK of c-fos leading to increased trrtn.srription. Here we provide evidence that phosphoryiatjon of CRKH by cAMP-dependent protein kinase (PKA) is required for the induction of c-fus expression by PTH. In UM R, 106-01 cells the PKC activator phorbol mylistate acetate and the cAMP analog 8-bromo-rAMP bol h induced the phosphorylation of CRKH while iononiycin did not, suggesting CREH is pbosphoryhited by PKA or PKC. 11-89. a specific inhibitor of PKA. inhibited pCRKU iormation and r-fos expression, whereas specific inhibitors of ralciuni/calniodulin dependent prolein kinases and PKC could not, Vsing various fragments of PTll wliich have been shown to activate different second messenger pathways. only PTH fragnieuls which can increa.se cAMP levels could increase both c-fos mRNA level and pCREB. Further, a c-fos promoter reporter plasrnid was cotransfected with increasing amounts of the human heat-.stable inhibitor of protein kinase A (PK'I). PTH-induced promoter activity was completely inhibited in a dose-dependent manner by PK1. In addition. GAL4-CREB chimeras were employed to eliminate the effects of endogenous CRKH. GAL4-CREB can confer PIH responsiveness to a he.terologous promoter, while a S133A mutant cannot. Taken together, these data provide strong evidence that PTH requires the activity of PKA to phosphoryiate CRKB at S 133 and increase levels of c-fos mKNA.

Original languageEnglish (US)
Pages (from-to)A1391
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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