Paz Cristina, Cornejo Maciel Fabiana, Gorostizaga Alejandra, Castillo Ana F, Mori Sequeiros García M Mercedes, Maloberti Paula M, Orlando Ulises D, Mele Pablo G, Poderoso Cecilia, Podesta Ernesto J
Departamento de Bioquímica Humana, Facultad de Medicina, Instituto de Investigaciones Biomédicas (INBIOMED), Universidad de Buenos Aires (UBA-CONICET) , Ciudad Autónoma de Buenos Aires , Argentina.
Front Endocrinol (Lausanne). 2016 Jun 9;7:60. doi: 10.3389/fendo.2016.00060. eCollection 2016.
In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinases is linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity are dependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics and cell proliferation are functions also associated with protein kinases. On the other hand, protein tyrosine dephosphorylation is an additional component of the ACTH signaling pathway, which involves the "classical" protein tyrosine phosphatases (PTPs), such as Src homology domain (SH) 2-containing PTP (SHP2c), and members of the MAP kinase phosphatase (MKP) family, such as MKP-1. PTPs are rapidly activated by posttranslational mechanisms and participate in hormone-stimulated steroid production. In this process, the SHP2 tyrosine phosphatase plays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonic acid (AA) release and StAR induction. In contrast, MKPs in steroidogenic cells have a role in the turn-off of the hormonal signal in ERK-dependent processes such as steroid synthesis and, perhaps, cell proliferation. This review analyzes the participation of these tyrosine phosphates in the ACTH signaling pathway and the action of kinases and phosphatases in the regulation of mitochondrial dynamics and steroid production. In addition, the participation of kinases and phosphatases in the signal cascade triggered by different stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed.
在肾上腺皮质细胞中，促肾上腺皮质激素（ACTH）可促进多种蛋白激酶的激活。这些激酶的作用主要通过类固醇生成急性调节蛋白（StAR）与类固醇生成相关联，StAR的表达和活性取决于基因组和非基因组水平的蛋白磷酸化事件。激素依赖性线粒体动力学和细胞增殖也是与蛋白激酶相关的功能。另一方面，蛋白酪氨酸去磷酸化是ACTH信号通路的一个额外组成部分，涉及“经典”蛋白酪氨酸磷酸酶（PTP），如含Src同源结构域（SH）2的PTP（SHP2c），以及丝裂原活化蛋白激酶磷酸酶（MKP）家族的成员，如MKP-1。PTP通过翻译后机制迅速激活，并参与激素刺激的类固醇生成。在此过程中，SHP2酪氨酸磷酸酶在一个包含酰基辅酶A合成酶-4（Acsl4）、花生四烯酸（AA）释放和StAR诱导的机制中起关键作用。相反，类固醇生成细胞中的MKP在依赖ERK的过程（如类固醇合成，可能还有细胞增殖）中激素信号的关闭中发挥作用。本综述分析了这些酪氨酸磷酸酶在ACTH信号通路中的参与情况，以及激酶和磷酸酶在调节线粒体动力学和类固醇生成中的作用。此外，还将其他类固醇生成组织中不同刺激引发的信号级联反应中激酶和磷酸酶的参与情况与肾上腺皮质细胞/ACTH进行了比较并讨论。
