Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells.
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.
Musnier
Astrid
A
Unité Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France.
Heitzler
Domitille
D
Boulo
Thomas
T
Tesseraud
Sophie
S
Durand
Guillaume
G
Lécureuil
Charlotte
C
Guillou
Hervé
H
Poupon
Anne
A
Reiter
Eric
E
Crépieux
Pascale
P
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003198:Computer Simulation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000737:chemistry / Q000378:metabolism*; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D002867:Chromones; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D043562:Receptors, G-Protein-Coupled; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005640:Follicle Stimulating Hormone; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D017868:Cyclic AMP-Dependent Protein Kinases