Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen-activated protein kinase in GH3 pituitary cells

R. Steinmetz, P. Zeng, D. W. King, Emily Walvoord, O. H. Pescovitz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Posttranslational processing of the pro-growth hormone-releasing hormone (proGHRH) peptide can result in the formation of at least two peptide products: GHRH and the C-terminal peptide, GHRH-related peptide (GHRH-RP). While cyclic adenosine monophosphate transduces many of the actions of GHRH, other pathways also have been implicated in its actions. The aims of this study were to examine and characterize the activation of mitogen-activated protein kinase (MAPK) pathways by GHRH, and GHRH-RP in pituitary-derived GH3 cells, as well as the activation of the transcription factors that serve as substrates for these kinases. GHRH rapidly increased p44/p42 MAPK activity in GH3 cells in a protein kinase A-dependent and a protein kinase C-independent manner and stimulated the activation of the transcription factor Elk-1. By contrast, GHRH-RP and p75-92NH2 had no effect on p44/p42 MAPK phosphorylation in these cells. Additionally, we determined that all three peptides, GHRH, GHRH-RP, and p75-92NH2, rapidly and specifically increase phosphorylation of p38 MAPK and stimulate the activation of the nuclear factor CHOP. These are the first studies to demonstrate the activation of Elk-1 by GHRH and the activation of p38 MAPK and CHOP by GHRH, GHRH-RP, and p75-92NH2. We conclude that members of the GHRH family of peptides differentially activate multiple intracellular signaling pathways and suggest that the biologic actions of GHRH may be far more diverse than previously thought.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalEndocrine
Volume15
Issue number1
DOIs
StatePublished - 2001

Fingerprint

Growth Hormone-Releasing Hormone
p38 Mitogen-Activated Protein Kinases
Peptides
Mitogen-Activated Protein Kinase 1
ets-Domain Protein Elk-1
Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Cyclic AMP
Protein Kinase C
Transcription Factors
Phosphotransferases
growth hormone releasing hormone-related peptide

Keywords

  • GH cells
  • GHRH
  • Growth hormone-releasing hormone related peptide
  • MAPK
  • Signal transduction

ASJC Scopus subject areas

  • Endocrinology

Cite this

Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen-activated protein kinase in GH3 pituitary cells. / Steinmetz, R.; Zeng, P.; King, D. W.; Walvoord, Emily; Pescovitz, O. H.

In: Endocrine, Vol. 15, No. 1, 2001, p. 119-127.

Research output: Contribution to journalArticle

Steinmetz, R. ; Zeng, P. ; King, D. W. ; Walvoord, Emily ; Pescovitz, O. H. / Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen-activated protein kinase in GH3 pituitary cells. In: Endocrine. 2001 ; Vol. 15, No. 1. pp. 119-127.
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