Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8476528 | Molecular and Cellular Endocrinology | 2018 | 29 Pages |
Abstract
The role of protein kinase C (PKC) isoforms (PKCs) in GnRH-stimulated MAPK [ERK1/2, JNK1/2 and p38) phosphorylation was examined in gonadotrope derived cells. GnRH induced a protracted activation of ERK1/2 and a slower and more transient activation of JNK1/2 and p38MAPK. Gonadotropes express conventional PKCα and PKCβII, novel PKCδ, PKCε and PKCθ, and atypical PKC-ι/λ. The use of green fluorescent protein (GFP)-PKCs constructs revealed that GnRH induced rapid translocation of PKCα and PKCβII to the plasma membrane, followed by their redistribution to the cytosol. PKCδ and PKCε localized to the cytoplasm and Golgi, followed by the rapid redistribution by GnRH of PKCδ to the perinuclear zone and of PKCε to the plasma membrane. 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 ERK1/2, JNK1/2 and 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 MAPKs phosphorylation may be explained by persistent vs. transient redistribution of selected PKCs or redistribution of a given PKC to the perinuclear zone vs. the plasma membrane. Thus, we have identified the PKCs involved in GnRH stimulated MAPKs phosphorylation in gonadotrope derived cells. Once activated, the MAPKs will mediate the transcription of the gonadotropin subunits and GnRH receptor genes.
Keywords
cPKCPKCεPLDphorbol 12-myristate 13-acetateGnRHRPKCαJun N-terminal kinaseaPKCPKCδPhospholipase C-βPLA2RFPGonadotropesPKCβIIFSHβPKCsGnRHlhβnPKCGPCRGFPPLCβp38ERKJnkPKCG-protein coupled receptorPMAMAPKphospholipase A2PKC isoformsstandard error of meandiacylglycerolDAGdominant negativePhosphatidylserinePhospholipase DSEMhemagglutinin epitopegonadotropin releasing hormonefollicle stimulating hormoneluteinizing hormoneFSHG-proteinguanine nucleotide binding proteingreen fluorescent proteinred fluorescent proteinProtein kinase Cmitogen-activated protein kinaseextracellular signal-regulated kinasegonadotropin releasing hormone receptor
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Authors
Shany Mugami, Masha Dobkin-Bekman, Liat Rahamim-Ben Navi, Zvi Naor,