Differential Role of PKC Isoforms in GnRH and Phorbol 12-Myristate 13-Acetate Activation of Extracellular Signal-Regulated Kinase and Jun N-Terminal Kinase

作者：Dobkin Bekman Masha; Ben Navi Liat Rahamim; Shterntal Boris; Sviridonov Ludmila; Przedecki Fiorenza; Naidich Exler Michal; Brodie Chaya; Seger Rony; Naor Zvi^*

来源：Endocrinology, 2010, 151(10): 4894-4907.

DOI：10.1210/en.2010-0114

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 alpha T3-1 and L beta T2 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 PKC alpha and conventional PKC beta II, novel PKC delta, novel PKC epsilon, and novel PKC theta, and atypical PKC-(sic)lambda. The use of green fluorescent protein-PKC constructs revealed that GnRH induced rapid translocation of PKC alpha and PKC beta II to the plasma membrane, followed by their redistribution to the cytosol. PKC delta and PKC epsilon localized to the cytoplasm and Golgi, followed by the rapid redistribution by GnRH of PKC delta to the perinuclear zone and of PKC epsilon to the plasma membrane. Interestingly, PKC alpha, PKC beta II, and PKC epsilon 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 PKC beta II, PKC delta, and PKC epsilon mediate ERK2 activation by GnRH, whereas PKC alpha, PKC beta II, PKC delta, and PKC epsilon mediate ERK2 activation by PMA. Also, PKC alpha, PKC beta II, PKC delta, and PKC epsilon 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. (Endocrinology 151: 4894-4907, 2010)

• 出版日期2010-10