Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation.
Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation.
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DOI：
10.1038/srep28132
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发表时间：
2016-06-21
影响因子：
4.6
通讯作者：
Zeleznik AJ
中科院分区：
文献类型：
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作者：
Puri P;Little-Ihrig L;Chandran U;Law NC;Hunzicker-Dunn M;Zeleznik AJ
促卵泡激素（FSH）激活蛋白激酶A（PKA）可转导驱动卵巢颗粒细胞（GC）分化的信号。一个尚未解决的问题是PKA是否足以启动GC对FSH反应的复杂程序。我们比较了用FSH刺激或表达PKA-CQR（PKA的组成型活性突变体）的GC的信号通路和基因表达谱。FSH和PKA-CQR均刺激已知参与GC分化的蛋白质的磷酸化，包括CREB、β-连环蛋白、AKT、p42/44 MAPK、GAB 2、GSK-3 β、FOXO 1和雅普。与此相反，FSH刺激p38 MAP激酶的磷酸化，但PKA-CQR没有。微阵列分析显示，85%的转录本，由FSH上调增加到相当程度的PKA-CQR和由FSH下调的转录本，76%也下调PKA-CQR。FSH和PKA-CQR类似调节的转录物参与类固醇生成和分化，而PKA-CQR更强烈上调的转录物参与排卵。因此，PKA，在我们的实验方法的条件下，似乎作为一个主上游激酶，足以启动复杂的模式的细胞内信号传导途径和基因表达谱，伴随GC分化。
Activation of protein kinase A (PKA) by follicle stimulating hormone (FSH) transduces the signal that drives differentiation of ovarian granulosa cells (GCs). An unresolved question is whether PKA is sufficient to initiate the complex program of GC responses to FSH. We compared signaling pathways and gene expression profiles of GCs stimulated with FSH or expressing PKA-CQR, a constitutively active mutant of PKA. Both FSH and PKA-CQR stimulated the phosphorylation of proteins known to be involved in GC differentiation including CREB, ß-catenin, AKT, p42/44 MAPK, GAB2, GSK-3ß, FOXO1, and YAP. In contrast, FSH stimulated the phosphorylation of p38 MAP kinase but PKA-CQR did not. Microarray analysis revealed that 85% of transcripts that were up-regulated by FSH were increased to a comparable extent by PKA-CQR and of the transcripts that were down-regulated by FSH, 76% were also down-regulated by PKA-CQR. Transcripts regulated similarly by FSH and PKA-CQR are involved in steroidogenesis and differentiation, while transcripts more robustly up-regulated by PKA-CQR are involved in ovulation. Thus, PKA, under the conditions of our experimental approach appears to function as a master upstream kinase that is sufficient to initiate the complex pattern of intracellular signaling pathway and gene expression profiles that accompany GC differentiation.