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. (5th January 2017)

• Record Type: Journal Article
• Authors: Mugami, Shany; Kravchook, Shani; Rahamim-Ben Navi, Liat; Seger, Rony; Naor, Zvi
• Is Part Of: Molecular and cellular endocrinology. Volume 439(2017)
• Page Start: 141
• Page End: 154
• Publication Date: 2017-01-05
• Subjects: GnRH -- PKCα -- PKCβII -- PKCδ -- PKCε -- MAPKs -- p38 -- Gonadotropes -- αT3-1 and LβT2 cells; CaMK calmodulin-dependent protein kinase -- DAG diacylglycerol -- ERK extracellular-signal-regulated kinases -- GnRH gonadotropin-releasing hormone -- GnRHR gonadotropin-releasing hormone receptor -- IP3 inositol 1, 4, 5 trisphosphate -- JNK c-Jun N-terminal kinases -- MAPK mitogen-activated protein kinase -- PKC protein kinase C -- PKCs protein kinase C isoforms -- PMA phorbol 12-myristate 13-acetate -- PLA2 phospholipase A2 -- PLD phospholipase D -- PS phosphatidylserine -- RACKs receptors for activated C kinase -- VGCCs voltage-gated Ca2+ channels; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.10.031
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: We examined the role of PKCs and Ca 2+ 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 Ca 2+ influx via voltage-gated Ca 2+ channels and Ca 2+ mobilization, while in the differentiated LβT2 gonadotrope cells it is mediated only by Ca 2+ 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 Ca 2+ pools involved in GnRH stimulated p38MAPK phosphorylation. Highlights: GnRH and PMA stimulate p38MAPK phosphorylation in αT3-1 and LβT2 gonadotrope cells. Selective PKCs play a role in p38MAPK phosphorylation in a ligand-and cell context-dependent manner. Different Ca 2 pools play a role in p38MAPK phosphorylation in αT3-1 vs. LβT2 cells.