title: Differential role of PKC isoforms in GnRH and phorbol 12-myristate 13-acetate activation of extracellular signal-regulated kinase and Jun N-terminal kinase.
abstract: GnRH is the first key hormone of reproduction. The role of protein kinase C (PKC) isoforms in GnRH-stimulated MAPK [ERK and Jun N-terminal kinase (JNK)] was examined in the αT3-1 and LβT2 gonadotrope cells. Incubation of the cells with GnRH resulted in a protracted activation of ERK1/2 and a slower and more transient activation of JNK1/2. Gonadotropes express conventional PKCα and conventional PKCβII, novel PKCδ, novel PKCε, and novel PKCθ, and atypical PKC-ι/λ. The use of green fluorescent protein-PKC 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. Interestingly, PKCα, PKCβII, and PKCε translocation to the plasma membrane was more pronounced and more prolonged in phorbol-12-myristate-13-acetate (PMA) than in GnRH-treated cells. The use of selective inhibitors and dominant-negative plasmids for the various PKCs has revealed that PKCβII, PKCδ, and PKCε mediate ERK2 activation by GnRH, whereas PKCα, PKCβII, PKCδ, and PKCε mediate ERK2 activation by PMA. Also, PKCα, PKCβII, PKCδ, and PKCε are involved in GnRH and PMA stimulation of JNK1 in a cell-context-dependent manner. We present preliminary evidence that persistent vs. transient redistribution of selected PKCs or redistribution of a given PKC to the perinuclear zone vs. the plasma membrane may dictate its selective role in ERK or JNK activation. Thus, we have described the contribution of selective PKCs to ERK and JNK activation by GnRH.
authors.affiliation: Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Masha
authors.initials: M
authors.lastname: Dobkin-Bekman
authors.forename: Liat
authors.initials: L
authors.lastname: Rahamin-Ben Navi
authors.forename: Liat Rahamim
authors.initials: LR
authors.lastname: Ben-Navi
authors.forename: Boris
authors.initials: B
authors.lastname: Shterntal
authors.forename: Ludmila
authors.initials: L
authors.lastname: Sviridonov
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Przedecki
authors.forename: Michal
authors.initials: M
authors.lastname: Naidich-Exler
authors.forename: Chaya
authors.initials: C
authors.lastname: Brodie
authors.forename: Rony
authors.initials: R
authors.lastname: Seger
authors.forename: Zvi
authors.initials: Z
authors.lastname: Naor
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D007987:Gonadotropin-Releasing Hormone; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate