Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins but also through β-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT(1A)R) in human embryonic kidney (HEK)293 cells.
View Article and Find Full Text PDFThe injection of equine chorionic gonadotropin (eCG) in dairy goats induces the production of anti-eCG antibodies (Abs) in some females. We have previously shown that Abs negatively modulate the LH and FSH-like bioactivities of eCG, in most cases, compromising fertility in treated females. Surprisingly, we found out that some anti-eCG Abs improved fertility and prolificity of the treated females, in vivo.
View Article and Find Full Text PDFFSH-receptor (FSH-R) signaling is regulated by agonist-induced desensitization and internalization. It has been shown, in a variety of overexpression systems, that G protein-coupled receptor kinases (GRKs) phosphorylate the activated FSH-R, promote beta-arrestin recruitment and ultimately lead to internalization. The accuracy of this mechanism has not yet been demonstrated in cells expressing these different molecules at physiological levels.
View Article and Find Full Text PDFClassically, the FSH receptor (FSH-R) mediates its effects through coupling to guanine nucleotide-binding protein alpha S subunit (Galpha(s)) and activation of the cAMP/protein kinase A (PKA) signaling pathway. beta-Arrestins are rapidly recruited to the FSH-activated receptor and play key roles in its desensitization and internalization. Here, we show that the FSH-R expressed in HEK 293 cells activated ERK by two temporally distinct pathways dependent, respectively, on Galpha(s)/PKA and beta-arrestins.
View Article and Find Full Text PDFBackground: The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood.
View Article and Find Full Text PDFThe testis is devoted to two important tasks: haploid cell production and sexual steroid synthesis. A number of highly sophisticated and unique strategies operate during spermatogenesis, a process crucial for reproduction, heredity and evolution. It is particularly important to decipher the underlying molecular mechanisms whose function can be perverted in pathological situations, such as infertility and testicular cancers, which represent an increasing biomedical issue today.
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