How Protein Kinase A Activates Canonical Tyrosine Kinase Signaling Pathways To Promote Granulosa Cell Differentiation

Law, Nathan C.; Donaubauer, Elyse M.; Zeleznik, Anthony J.; Hunzicker-Dunn, Mary

doi:10.1210/en.2017-00163

Cited by 34 publications

(25 citation statements)

References 59 publications

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“…The myosin-phosphatase 1 (MYPT1) is a protein made up by three subunits: the PP1c, a targeting/regulatory subunit and a 20kDa subunit of unknown function called M20 [11,12]. PP1 and MYPT1 have been found to be associated with IRS1 in mouse granulosa cells [13]. Furthermore, PKA is known to activate PP1 through MYPT1 phosphorylation [13].…”

Section: Introductionmentioning

confidence: 99%

“…PP1 and MYPT1 have been found to be associated with IRS1 in mouse granulosa cells [13]. Furthermore, PKA is known to activate PP1 through MYPT1 phosphorylation [13]. Incubation with tautomycim, a selective PP1β inhibitor, has been shown to inhibit FSH-mediated IRS1 phosphorylation, in the presence of endogenous IGF1 in granulosa cells [8].…”

Section: Introductionmentioning

confidence: 99%

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The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

Cannarella

Arato

Condorelli

et al. 2019

JCM

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Experimental evidence has shown that the IGF1 receptor (IGF1R) is involved in testicular development during embryogenesis. More recently, data gathered from mice granulosa cells and zebrafish spermatogonia suggest that IGF1R has a role in Follicle-stimulating hormone (FSH) signaling. No evidence has been reported on this matter in Sertoli cells (SCs) so far. The aim of the study was to evaluate the role, if any, of the IGF1R in FSH signaling in SCs. The effects of FSH exposure on myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT308, AKT473, c-Jun N-terminal kinase (JNK) phosphorylation and on anti-Müllerian hormone (AMH), inhibin B and FSH receptor (FSHR) mRNA levels were assessed with and without the IGF1R inhibitor NVP-AEW541 in purified and functional porcine neonatal SCs. Pre-treatment with NVP-AEW541 inhibited the FSH-induced MYPT1 and ERK 1/2 phosphorylation, decreased the FSH-dependent Protein kinase B (AKT)308 phosphorylation, but did not affect the FSH-induced AKT473 and JNK phosphorylation rate. It also interfered with the FSH-induced AMH and FSHR down-regulation. No influence was observed on the FSH-stimulated Inhibin B gene expression. Conclusion. These findings support the role of theIGF1R in FSH signaling in porcine SCs. The possible influence of IGF1 stimulation on the FSH-mediated effects on SCs should be further explored.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

Cannarella

Arato

Condorelli

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…Therefore, both IGF-1 and IGF-1R can directly modulate specific aspects of cognition and memory function in the hippocampus (Sonntag et al, 2005 ; Deak and Sonntag, 2012 ). IGF-1-mediated activation of neurotropin receptors, and IGF-1R activation (by IGF-1 or insulin) involves signaling of downstream proteins (Hiney et al, 2009 ; Liu et al, 2015 ; Law et al, 2017 ). These kinases are involved in several pathways associated with synaptic function, growth, inflammation and metabolism (Schumacher et al, 1991 ; Mynarcik et al, 1997 ; Siddle, 2011 ; Fernandez and Torres-Alemán, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

A Putative Mechanism of Age-Related Synaptic Dysfunction Based on the Impact of IGF-1 Receptor Signaling on Synaptic CaMKIIα Phosphorylation

et al. 2018

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Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways. These proteins (CaMKIIα and MAPK) regulate Ca2+ movement and long-term potentiation (LTP). Since IGF-1R controls the synaptic activity of Ca2+, CaMKIIα and MAPK signaling, the possible mechanism through which an age-dependent change in IGF-1R can alter the synaptic expression and phosphorylation of these proteins in aging needs to be investigated. In this study, we evaluated the relationship between an age-dependent change in brain IGF-1R and phosphorylation of CaMKIIα/MAPK. Furthermore, we elucidated possible mechanisms through which dysregulated CaMKIIα/MAPK interaction may be linked to a change in neurotransmitter processing and synaptic function. Male C57BL/6 VGAT-Venus mice at postnatal days 80 (P80), 365 and 730 were used to study age-related neural changes in two brain regions associated with cognitive function: hippocampus and prefrontal cortex (PFC). By means of high throughput confocal imaging and quantitative immunoblotting, we evaluated the distribution and expression of IGF-1, IGF-1R, CaMKIIα, p-CaMKIIα, MAPK and p-MAPK in whole brain lysate, hippocampus and cortex. Furthermore, we compared protein expression patterns and regional changes at P80, P365 and P730. Ultimately, we determined the relative phosphorylation pattern of CaMKIIα and MAPK through quantification of neural p-CaMKIIα and p-MAPK/ErK, and IGF-1R expression for P80, P365 and P730 brain samples. In addition to a change in synaptic function, our results show a decrease in neural IGF-1/IGF-1R expression in whole brain, hippocampus and cortex of aged mice. This was associated with a significant upregulation of phosphorylated neural MAPK (p-MAPK) and decrease in total brain CaMKIIα (i.e., CaMKIIα and p-CaMKIIα) in the aged brain. Taken together, we showed that brain aging is associated with a change in neural IGF-1/IGF-1R expression and may be linked to a change in phosphorylation of synaptic kinases (CaMKIIα and MAPK) that are involved in the modulation of LTP.

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“…The phosphorylated IRS1 enhances PI3K/AKT cascade, which is responsible for synergic gene response to IGF1 and FSH (Law & Hunzicker‐Dunn, ). Consistent with these results, in granulosa cells, the concomitant exposure to exogenous FSH and IGF1 was shown to induce IRS1 phosphorylation, leading to the transcription of common FSH‐ and IGF1‐induced genes and to granulosa cell differentiation (Law et al ., ). Therefore, in vitro studies on human SCs and GCs are needed to show whether this pathway occurs also in men.…”

Section: Discussionmentioning

confidence: 97%

Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

et al. 2017

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SUMMARYWe recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans. In animals, IGF1/IGF1R has been found to be involved in testicular development during embryogenesis, in Sertoli cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation. Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular volume. The molecular pathways responsible for testicular differentiation and IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF system may be involved in FSH signaling also in humans. We suggest a possible molecular pathway occurring in human SCs, which involves both IGF1 and FSH through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH-induced effects may open new ways for a targeted therapy in idiopathic non-FSH-responder oligoasthenoteratozoospermia.

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How Protein Kinase A Activates Canonical Tyrosine Kinase Signaling Pathways To Promote Granulosa Cell Differentiation

Cited by 34 publications

References 59 publications

The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

A Putative Mechanism of Age-Related Synaptic Dysfunction Based on the Impact of IGF-1 Receptor Signaling on Synaptic CaMKIIα Phosphorylation

Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

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