Musnier Astrid, Heitzler Domitille, Boulo Thomas, Tesseraud Sophie, Durand Guillaume, Lécureuil Charlotte, Guillou Hervé, Poupon Anne, Reiter Eric, Crépieux Pascale
Unité Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France.
Cell Mol Life Sci. 2009 Nov;66(21):3487-503. doi: 10.1007/s00018-009-0134-z.
The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined, in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages. In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424, through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which led to experimentally inaccessible predictions on p70S6K phosphorylation rate.
与酪氨酸激酶受体（TKR）不同，G蛋白偶联受体（GPCR）激活参与mRNA翻译的信号通路的机制尚不明确。我们比较了内源性表达的一种GPCR和一种TKR在两个发育阶段对原代大鼠支持细胞中70 kDa核糖体S6激酶p70S6K磷酸化的介导能力。在用促卵泡激素（FSH）刺激的增殖细胞中，活性p70S6K在T389和T421/S424位点发生磷酸化，这是通过环磷酸腺苷依赖性激酶（PKA）和磷脂酰肌醇-3激酶（PI3K）的拮抗作用实现的。在用FSH刺激的分化细胞中，活性p70S6K仅在T389位点发生磷酸化，PKA和PI3K独立增强其活性。在两个发育阶段，胰岛素诱导的p70S6K调节与报道的数据一致。因此，TKR和GPCR触发不同的p70S6K活性构象。p70S6K的发育调节在一个拟合数据的动态数学模型中得以形式化，该模型对p70S6K磷酸化速率做出了实验上难以获得的预测。
