Beta 2-adrenoreceptors stimulate c-fos transcription through multiple cyclic AMP- and Ca(2+)-responsive elements in cerebellar granular neurons.

Abstract:

:Neurons from the granular layer of the cerebellum express functional beta 2-adrenoreceptors (beta 2-ARs). We show that stimulation of beta 2-ARs with isoprenaline increases cyclic AMP (cAMP) production and stimulates transcription of genes containing the cAMP-responsive element (CRE; TGACGTCA). This effect is mediated by cAMP-dependent protein kinase and the trans-acting factor CRE binding protein. Transcriptional regulation by the beta 2-AR was investigated by using the c-fos protooncogene as a model system. We show that beta 2-ARs stimulate c-fos mRNA accumulation, increase AP1 binding activity, and stimulate transcription through the phorbol ester-responsive element (TGACTCA). The transcriptional regulation of c-fos itself was studied with reporter constructs driven by c-fos promoter sequences. Deletion studies revealed that beta 2-ARs stimulate c-fos transcription through at least three distinct regulatory sequences: (a) the CRE located at -60 bp 5' to the initiation site, (b) the fos AP1-like element (-291 to -297), and (c) the serum-responsive element (-297 to -317). The regulation of these elements by the two putative second messengers of the beta 2-AR, cAMP and Ca2+, was analyzed. We report that all three of these regulatory sequences are coregulated by both second messengers. These results indicate that beta 2-ARs stimulate c-fos transcription by multiple cAMP- and Ca(2+)-dependent regulatory elements in neurons.

journal_name

J Neurochem

authors

Barthel F,Loeffler JP

doi

10.1046/j.1471-4159.1995.64010041.x

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

41-51

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

64

pub_type

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