Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in lymphocytes

Diane R. Dowd, Jan S. Ryerse, Paul N. MacDonald, Roger Miesfeld, Merideth C. Kamradt

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In the WEHI7.2 thymoma cell line, cAMP, glucocorticoids, or increases in cytosolic Ca2+ concentration lead to cell death by apoptosis. In the present study, we examined the effects of these compounds on cAMP response element (CRE)-mediated gene expression. Thapsigargin and A23187 were employed to increase cytosolic Ca2+ levels and induce apoptosis. Both compounds enhanced transcription from a CRE preceding apoptotic death. Moreover, the transcriptional response to the combination of forskolin and either thapsigargin or A23187 was synergistic mirroring the effect on cell death. Importantly, dexamethasone treatment, which causes an efflux of Ca2+ from the ER, induced transcription from a CRE alone or in synergy with forskolin. The increase in CRE-controlled gene expression correlated with a decrease in cell viability. Following treatment with forskolin, thapsigargin, or dexamethasone, the CRE binding protein (CREB) was phosphorylated at levels correlating with the level of induced gene expression. These data suggest that transcriptional crosstalk between independent signaling pathways occurs in lymphocytes, and CREB may play a central role in the mediation of CRE-dependent transcription by these diverse set of apoptotic agents.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume128
Issue number1-2
DOIs
StatePublished - Apr 4 1997

Fingerprint

Lymphocytes
Response Elements
Crosstalk
Gene expression
Glucocorticoids
Thapsigargin
Gene Expression
Colforsin
Transcription
Calcimycin
Cell death
Dexamethasone
Cell Death
Cells
Apoptosis
Cyclic AMP Response Element-Binding Protein
Thymoma
Cell Survival
Carrier Proteins
Cell Line

Keywords

  • Apoptosis
  • Ca
  • cAMP
  • Cyclic AMP response element binding protein
  • Glucocorticoids

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in lymphocytes. / Dowd, Diane R.; Ryerse, Jan S.; MacDonald, Paul N.; Miesfeld, Roger; Kamradt, Merideth C.

In: Molecular and Cellular Endocrinology, Vol. 128, No. 1-2, 04.04.1997, p. 29-37.

Research output: Contribution to journalArticle

Dowd, Diane R. ; Ryerse, Jan S. ; MacDonald, Paul N. ; Miesfeld, Roger ; Kamradt, Merideth C. / Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in lymphocytes. In: Molecular and Cellular Endocrinology. 1997 ; Vol. 128, No. 1-2. pp. 29-37.
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