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Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2009 Nov; Vol. 66 (21), pp. 3487-503. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Cell Culture Techniques
Cell Differentiation drug effects
Cells, Cultured
Chromones pharmacology
Computer Simulation
Cyclic AMP-Dependent Protein Kinases metabolism
Follicle Stimulating Hormone pharmacology
Male
Morpholines pharmacology
Phosphorylation drug effects
Protein Conformation
Protein Kinase Inhibitors pharmacology
Rats
Rats, Wistar
Receptors, G-Protein-Coupled metabolism
Ribosomal Protein S6 Kinases, 70-kDa chemistry
Sertoli Cells drug effects
Sertoli Cells metabolism
Cell Differentiation physiology
Models, Biological
Receptors, G-Protein-Coupled physiology
Ribosomal Protein S6 Kinases, 70-kDa metabolism
Sertoli Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 66
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 19730801
- Full Text :
- https://doi.org/10.1007/s00018-009-0134-z