A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone α-subunit promoter by gonadotropin-releasing hormone

M. S. Roberson, A. Misra-Press, M. E. Laurance, Philip Stork, Richard Maurer

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195 Citations (Scopus)

Abstract

Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone α- subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK cascade by an expression vector for a constitutively active form of the Raf-1 kinase led to stimulation of the α-subunit promoter in a concentration-dependent manner. GnRH treatment was found to increase the phosphorylation of tyrosine residues of MAPK and to increase MAPK activity, as determined by an immune complex kinase assay. A reporter gene assay using the MAPK-responsive, carboxy-terminal domain of the Elk1 transcription factor was also consistent with GnRH-induced activation of MAPK. Interference with the MAPK pathway by expression vectors for kinase-defective MAPKs or vectors encoding MAPK phosphatases reduced the transcription-stimulating effects of GnRH. The DNA sequences which are required for responses to GnRH include an Ets factor-binding site. An expression vector for a dominant negative form of Ets-2 was able to reduce GnRH effects on expression of the α-subunit gene. These findings provide evidence that GnRH treatment leads to activation of the MAPK cascade in gonadotropes and that activation of MAPK contributes to stimulation of the α-subunit promoter. It is likely that an Ets factor serves as a downstream transcriptional effector of MAPK in this system.

Original languageEnglish (US)
Pages (from-to)3531-3539
Number of pages9
JournalMolecular and Cellular Biology
Volume15
Issue number7
StatePublished - 1995

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Mitogen-Activated Protein Kinases
Gonadotropin-Releasing Hormone
Glycoproteins
Hormones
ets-Domain Protein Elk-1
Mitogen-Activated Protein Kinase Phosphatases
Proto-Oncogene Proteins c-raf
Mitogen-Activated Protein Kinase Kinases
G-Protein-Coupled Receptors
Antigen-Antibody Complex
Reporter Genes
Tyrosine
Phosphotransferases
Binding Sites
Phosphorylation
Gene Expression

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone α-subunit promoter by gonadotropin-releasing hormone. / Roberson, M. S.; Misra-Press, A.; Laurance, M. E.; Stork, Philip; Maurer, Richard.

In: Molecular and Cellular Biology, Vol. 15, No. 7, 1995, p. 3531-3539.

Research output: Contribution to journalArticle

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