a mitochondrial kinase complex is essential to mediate an erk12-dependent phosphorylation of a key regulatory protein in steroid biosynthesis线粒体激酶复杂是至关重要的调解一个erk12-dependent类固醇生物合成的关键调控蛋白的磷酸化.pdfVIP

A Mitochondrial Kinase Complex Is Essential to Mediate an ERK1/2-Dependent Phosphorylation of a Key Regulatory Protein in Steroid Biosynthesis 1 2 1 1 1 2 1 Cecilia Poderoso , Daniela P. Converso , Paula Maloberti , Alejandra Duarte , Isabel Neuman , Soledad Galli , Fabiana Cornejo Maciel , Cristina 1 ´ 2,3 2 ´ 1 Paz , Marıa C. Carreras , Juan J. Poderoso , Ernesto J. Podesta * ´ 1 Instituto de Investigaciones Moleculares de Enfermedades Hormonales, Neurodegenerativas y Oncologicas (IIMHNO), Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina, 2 Laboratory of Oxygen Metabolism, University Hospital, University of Buenos Aires, Buenos Aires, Argentina, 3 Department of Clinical Biochemistry, University Hospital, University of Buenos Aires, Buenos Aires, Argentina ERK1/2 is known to be involved in hormone-stimulated steroid synthesis, but its exact roles and the underlying mechanisms remain elusive. Both ERK1/2 phosphorylation and steroidogenesis may be triggered by cAMP/cAMP-dependent protein kinase (PKA)-dependent and-independent mechanisms; however, ERK1/2 activation by cAMP results in a maximal steroidogenic rate, whereas canonical activation by epidermal growth factor (EGF) does not. We demonstrate herein by Western blot analysis and confocal studies that temporal mitochondrial ERK1/2 activation is obligatory for PKA-mediated steroidogenesis in the Leydig- transformed MA-10 cell line. PKA activity leads to the phosphorylation of a constitutive mitochondrial MEK1/2 pool with a lower effect in cytosolic MEKs, while EGF al