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Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2009

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

Résumé

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.

Dates et versions

hal-02660848 , version 1 (30-05-2020)

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Citer

Astrid Musnier, Domitille Heitzler, Thomas Boulo, Sophie Tesseraud, Guillaume Durand, et al.. Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells. Cellular and Molecular Life Sciences, 2009, 66 (21), pp.3487-3503. ⟨10.1007/s00018-009-0134-z⟩. ⟨hal-02660848⟩
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