Follicle-stimulating hormone activates p70 ribosomal protein S6 kinase by protein kinase A-mediated dephosphorylation of Thr 421/Ser 424 in primary Sertoli cells.
FSH is a major hormonal input that drives Sertoli cells to their fully differentiated function in male reproduction. It is a physiologically important issue to define how FSH mediates its effects at the cellular level to regulate gene expression. FSH biological activities are transduced via a seven-spanned transmembrane receptor, the FSH-R, primarily leading to cAMP-dependent protein kinase A (PKA) activation and cAMP response element binding protein-mediated transcriptional responses. Nevertheless, the intracellular mechanisms interacting with PKA to control Sertoli cell differentiation by FSH are still incompletely defined. Here, we report that, in primary cultures of Sertoli cells isolated from prepubertal rats, FSH enhanced p70S6K enzymatic activity, in a PKA-dependent manner. p70S6K was constitutively phosphorylated on Thr 389, in a manner sensitive to inhibitors of phosphatidyl-inositide-3 kinase and mammalian target of rapamycin. But FSH could not enhance p70S6K phosphorylation on Thr 389. Rather, the hormone induced the dephosphorylation of Thr 421/Ser 424, located in the autoinhibitory domain of p70S6K, in a PKA-dependent manner. Consistently, FSH-induced phosphorylation of the S6 ribosomal protein, a cellular substrate of p70S6K, required PKA activity. In conclusion, these results show that FSH triggers unexpected regulations of p70S6K by dephosphorylation of Thr 421/Ser 424 mediated by PKA, and stimulates S6 phosphorylation, in Sertoli cells.
Lécureuil
Charlotte
C
Laboratoire de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique/Centre National pour la Recherche Scientifique/Université de Tours/Haras Nationaux, Unité Mixte de Recherche 6175.
Tesseraud
Sophie
S
Kara
Elodie
E
Martinat
Nadine
N
Sow
Amina
A
Fontaine
Isabelle
I
Gauthier
Christophe
C
Reiter
Eric
E
Guillou
Florian
F
Crépieux
Pascale
P
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005640:Follicle Stimulating Hormone / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000201:enzymology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D013912:Threonine / Q000378:metabolism
D000081082:Phosphoinositide-3 Kinase Inhibitors; D013912:Threonine; D012694:Serine; D005640:Follicle Stimulating Hormone; D011494:Protein Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020123:Sirolimus