Differential roles of PKC isoforms (PKCs) and Ca2+ in GnRH and phorbol 12-myristate 13-acetate (PMA) stimulation of p38MAPK phosphorylation in immortalized gonadotrope cells

Shany Mugami, Shani Kravchook, Liat Rahamim-Ben Navi, Rony Seger, Zvi Naor

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the role of PKCs and Ca2+ in GnRH-stimulated p38MAPK phosphorylation in the gonadotrope derived αT3-1 and LβT2 cell lines. GnRH induced a slow and rapid increase in p38MAPK phosphorylation in αT3-1 and LβT2 cells respectively, while PMA gave a slow response. The use of dominant negatives for PKCs and peptide inhibitors for the receptors for activated C kinase (RACKs), has revealed differential role for PKCα, PKCβII, PKCδ and PKCε in p38MAPK phosphorylation in a ligand-and cell context-dependent manner. The paradoxical findings that PKCs activated by GnRH and PMA play a differential role in p38MAPK phosphorylation may be explained by differential localization of the PKCs. Basal, GnRH- and PMA- stimulation of p38MAPK phosphorylation in αT3-1 cells is mediated by Ca2+ influx via voltage-gated Ca2+ channels and Ca2+ mobilization, while in the differentiated LβT2 gonadotrope cells it is mediated only by Ca2+ mobilization. p38MAPK resides in the cell membrane and is relocated to the nucleus by GnRH (∼5 min). Thus, we have identified the PKCs and the Ca2+ pools involved in GnRH stimulated p38MAPK phosphorylation.

Original languageEnglish
Pages (from-to)141-154
Number of pages14
JournalMolecular and Cellular Endocrinology
Volume439
DOIs
StatePublished - 5 Jan 2017

Keywords

  • GnRH
  • Gonadotropes
  • MAPKs
  • PKCα
  • PKCβII
  • PKCδ
  • PKCε
  • p38
  • αT3-1 and LβT2 cells

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