Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells

作者：Musnier Astrid; Heitzler Domitille; Boulo Thomas; Tesseraud Sophie; Durand Guillaume; Lecureuil Charlotte; Guillou Herve; Poupon Anne; Reiter Eric; Crepieux Pascale^*

来源：Cellular and Molecular Life Sciences, 2009, 66(21): 3487-3503.

DOI：10.1007/s00018-009-0134-z

• p70S6K
• G protein-coupled receptor
• Dynamic model
• Differentiation

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.

• 出版日期2009-11